老化、がん

 

  1. How cancer develops (1:48) Bupa Health UK チャンネル登録者数 8.78万人
  2. Cancer, How Cancer Starts, How Cancer Spreads, Where and Why, Animation. (3:57) Alila Medical Media チャンネル登録者数 125万人
  3. Cancer Metabolism: From molecules to medicine (1:28:25) Harvard Medical School チャンネル登録者数 28.2万人
  4. DNA Methylation and Cancer – Garvan Institute (5:15) Garvan Institute of Medical Research チャンネル登録者数 1万人

内胚葉由来の器官の発生：消化管

消化器系の構造と機能

  1. Digestive system The Noted Anatomist チャンネル登録者数 55.6万人 (41:32) 非常に明解な説明。
  2. 肝臓はどのような構造になっているの？2016/12/29　看護roo! 肝小葉は肝臓全体で50万個ほどあります。肝小葉の周囲にあるグリソン鞘（しょう）には、門脈の枝である小葉間静脈、肝動脈の枝である小葉間動脈、胆汁を胆管に送り出す小葉間胆管が並び、この３つは肝３つ組とも呼ばれます。
  3. 胆のう　中外製薬　胆のうは、胆嚢（たんのう）と書きます。肝臓（かんぞう）で作られた胆汁（たんじゅう）を溜（た）めておくはたらきをしています。

消化管の発生に関する講義動画

  1. 2.9 Folding of the embryo Leiden Learning & Innovation Centre チャンネル登録者数 8.18万人 (6:42)
  2. Embryological Development of Gastro-Intestinal Tract – ACLAND (5:39) Rahell Omer チャンネル登録者数 1.56万人
  3. Gastrointestinal | Development & Embryology of the GI Tract: Part 1 (26:19) Ninja Nerd チャンネル登録者数 289万人

Role of HOX genes inGut development

 

肺の形成

The lung is composed of endoderm derived epithelial cells that constitute the luminal surface of the airways and alveolar spaces. Ensheathing the epithelium are mesenchymal derivatives including airway smooth muscle, pulmonary fibroblasts, and vascular endothelium. During development, the epithelium and mesenchyme are involved in a complex circuit of paracrine and autocrine signals that act to drive morphogenesis and patterning of the developing airway structure. The lung initially arises from the anterior foregut endoderm region, which itself arises from the definitive endoderm that develops soon after gastrulation. .

Citation:Lessons from development for directing lung endoderm differentiation in pluripotent stem cells Rachel S. Kadzik and Edward E. Morrisey Cell Stem Cell. Author manuscript; available in PMC 2013 Apr 6. Published in final edited form as: Cell Stem Cell. 2012 Apr 6; 10(4): 355–361. doi: 10.1016/j.stem.2012.03.013 PMCID: PMC3366272 NIHMSID: NIHMS367732 PMID: 22482501

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366272/

  1. Development of the Respiratory System | Stages of Lung Development | Embryology Byte Size Med (10:13) 最初に完成形を見せてから発生の話に入る順番が良い。

 

泌尿器・生殖器系の発生

腎の構造と機能

  1. 腎臓の解剖生理学

腎臓の形成、発生

Embryology | Development of the Urinary System Ninja Nerd (44:28) チャンネル登録者数 301万人

Development of the Kidneys | Renal Embryology | Development of the Urinary System | Embryology (5:30) Byte Size Med　チャンネル登録者数 10.7万人最初に完成形を見せてから発生の話に入る順番が良い。

ネフロンの形成メカニズム

In response to a signal from the ureter 尿管, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development. (Nature . 1994 Dec 15;372(6507):679-83. doi: 10.1038/372679a0. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4 K Stark 1, S Vainio, G Vassileva, A P McMahon https://pubmed.ncbi.nlm.nih.gov/7990960/)

男性生殖器、女性生殖器の発生

内性器は「ミュラー管」（卵管や子宮になる）と「ウォルフ管」（精管や精嚢になる）が起源となります。医師国家試験の時に「男はオオカミだからウルフ（ウォルフ管）、女性は鏡を見るからミラー（ミューラー管）」なんて覚えましたね！

https://medical-tribune.co.jp/rensai/articles/?blogid=11&entryid=564331

 

  1. One Tool for Many Jobs: Divergent and Conserved Actions of Androgen Signaling in Male Internal Reproductive Tract and External Genitalia REVIEW article Front. Endocrinol., 30 June 2022 Sec. Reproduction Volume 13 – 2022 | https://doi.org/10.3389/fendo.2022.910964
  2. Development of the Human Penis and Clitoris　Differentiation. 2018 Sep-Oct; 103: 74–85. Published online 2018 Aug 23. doi: 10.1016/j.diff.2018.08.001 PMCID: PMC6234061 An external file that holds a picture, illustration, etc. Object name is nihms-1504410-f0002.jpg
  3. The cell biology and molecular genetics of Müllerian duct development January 2018　Wiley Interdisciplinary Reviews: Developmental Biology 7(2):e310 DOI:10.1002/wdev.310 ResearchGate
  4. Herrera AM, Cohn MJ. Embryonic origin and compartmental organization of the external genitalia. Sci Rep. 2014 Nov 5;4:6896. doi: 10.1038/srep06896. PMID: 25372631; PMCID: PMC4894444. the genital tubercle, the precursor of the penis and clitoris, arises from two populations of progenitor cells that originate at the lateral edges of the embryo, at the level of the posterior hindlimb buds and anterior tail. During body wall closure, the left and right external genital progenitor pools are brought together at the ventral midline, where they form the paired genital swellings that give rise to the genital tubercle.
  5. Lin C, Yin Y, Veith GM, Fisher AV, Long F, Ma L. Temporal and spatial dissection of Shh signaling in genital tubercle development. Development. 2009 Dec;136(23) 3959-3967. doi:10.1242/dev.039768. PMID: 19906863; PMCID: PMC2778743.
  6. HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia Carley A. Shaut, Chie Saneyoshi, Emily A. Morgan, Wendy M. Knosp, Diane R. Sexton, H. Scott Stadler 15 February 2007 https://doi.org/10.1002/dvdy.21077
  7. Unique functions of Sonic hedgehog signaling during external genitalia
    development　２００１ ResearchGate

陰茎の長さと指の長さとの関連、生殖器と手の形成の関連

  1. Length of fingers and penis are related through fetal Hox gene expression Martin Voracek, D.Sc. John T. Manning, Ph.D. LETTER TO THE EDITOR Urology VOLUME 62, ISSUE 1, P201, JULY 2003  DOI:https://doi.org/10.1016/S0090-4295(02)02598-0
  2. Mortlock, D., Innis, J. Mutation of HOXA13 in hand-foot-genital syndrome . Nat Genet 15, 179–180 (1997). https://doi.org/10.1038/ng0297-179 We report the identification of a HOXA13 nonsense mutation in a family with hand-foot-genital syndrome.
  3. Hand-foot-genital syndrome Variants (also called mutations) in the HOXA13 gene cause hand-foot-genital syndrome. The HOXA13 gene provides instructions for producing a protein that plays an important role in development before birth. Specifically, this protein appears to be critical for the formation and development of the limbs (particularly the hands and feet), urinary tract, and reproductive system.

男性生殖器、女性生殖器の形成　講義動画

  1. Cincinnati University Reproductive Physiology Lecture 2 Determination of Sex(0:58) Errors in Gonadal Differentiation and Development (True hermaphroditism)(1:47) Lecture 5  Spermatogenesis (2:45) Lecture 6 Formation of the Placenta (1:09)

陰茎骨について

  1. なぜ人間のペニスには「骨」がないのか？　2016年12月15日 21時00分　Ｇｉｇａｚｉｎｅ　最初に陰茎骨を獲得した動物が誕生したのは1億4500万年前から9500万年前の間で、すべての霊長類と肉食動物に共通する祖先が陰茎骨を持っていたことが分かっています。現代でも多くのほ乳類や、人間に近いチンパンジーやボノボなどの霊長類が陰茎骨を持ち合わせており、むしろ人間は例外的な部類に含まれます。
  2. Epithelial-Mesenchymal Interactions in Development of the Mouse Fetal Genital Tubercle Eric A. Kurzrock; Laurence S. Baskin; Yingwu Li; Gerald R. Cunha Cells Tissues Organs (1999) 164 (3): 125–130　The mesenchyme of the adult mouse penis consists of a corpus cavernosum and proximal and distal bones. The differentiation of penile mesenchyme into bone and cartilage begins after birth and can be accelerated by androgens.

幹細胞、再生医療

iPS cells

iPS was first made from skin cells. Any cells can be used but now routinely iPS cells can be produced from blood samples (lymphocytes are used).

A New Era of Medicine with iPS Cells – Lecture by Professor Shinya Yamanaka NobelPrizeII チャンネル登録者数 1.5万人

4 genes Yamanaka used for his paper: Oct3/4, Sox2, Klf4, c-Myc (later he found that c-Myc was not needed)

  1. A New Era of Medicine with iPS Cells – Lecture by Professor Shinya Yamanaka (1:17:29) NobelPrizeII チャンネル登録者数 1.5万人
  2. Induction of Pluripotency by Defined Factors (1:09:50) NIH VideoCast チャンネル登録者数 3.92万人 NIH Director’s Wednesday Afternoon Lectures Air date: Thursday, January 14, 2010, 3:00:00 PM

Review articles

  1. Review Article GLIS1-3: emerging roles in reprogramming, stem and progenitor cell differentiation and maintenance David W. Scoville, Hong Soon Kang, Anton M. Jetten Published: 27 September 2017. doi: 10.21037/sci.2017.09.01 The GLI Similar 1-3 (GLIS) proteins form a subfamily of Krüppel-like zinc finger transcription factors that are closely-related to the GLI and ZIC subfamilies (1–8). Members of these three subfamilies share a highly homologous DNA binding domain (DBD) consisting of five Cys2His2-type zinc finger motifs. However, these proteins exhibit little homology outside their DBD region. … Initial overexpression of OCT3/4 (POU5F1), SOX2, and KLF4 (OSK) are widely used for the reprogramming of somatic cells into iPSCs (32). However, the efficiency of generating iPSCs is very low, which has been attributed to difficulties in overcoming epigenetics barriers in the starting cell (33). Co-expression of C-MYC increases the efficiency, but also enhances the potential tumorigenicity of iPSC-derived differentiated cells. Recently, using a screen analyzing 1,437 transcription factors for their ability to promote reprogramming efficiency, GLIS1 was found to greatly enhance the number of iPSC colonies generated when co-expressed with OSK (referred to as OSKG) in either human or mouse dermal fibroblasts (29,34). Inversely, down-regulation of GLIS1 expression by shRNAs reduced the OSK-induced generation of iPSC colonies in mouse fibroblasts suggesting that endogenous GLIS1 is able to promote OSK-mediated reprogramming.
  2. Ye L, Swingen C, Zhang J. Induced pluripotent stem cells and their potential for basic and clinical sciences. Curr Cardiol Rev. 2013 Feb 1;9(1):63-72. doi: 10.2174/157340313805076278. PMID: 22935022; PMCID: PMC3584308. Later, it was shown that iPS cells can be generated from fibroblasts by viral integration of Oct4/Sox2/Klf4 without c-Myc []. Although these iPS cells showed reduced tumorigenicity in chimeras and progeny mice, the reprogramming process is much slower, and efficiency is substantially reduced.
  3. Schmidt R, Plath K. The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation. Genome Biol. 2012 Oct 22;13(10):251. doi: 10.1186/gb-2012-13-10-251. PMCID: PMC3491406. The most well known of these enhancer factors is c-Myc, which was added alongside O, S and K in the original reprogramming experiment but later shown to be dispensible [,,,,,].
  4. Takahashi K, Mitsui K, Yamanaka S. Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature. 2003 May 29;423(6939):541-5. doi: 10.1038/nature01646. PMID: 12774123. (Yamanaka moved to Kyoto University in 2005. Yamanaka asked Kazu Takahashi to take over the project (24 candidate genes for reprogramming). Yamanaka knew that the project was risky but thought it was ok for the next a couple of years without papers as Takahashi published this Nature paper.(https://www.youtube.com/watch?v=AD1sZU1yk-Y 33:07))

Original articles

  1. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1 Momoko Maekawa, Kei Yamaguchi, Tomonori Nakamura, Ran Shibukawa, Ikumi Kodanaka, Tomoko Ichisaka, Yoshifumi Kawamura, Hiromi Mochizuki, Naoki Goshima, and Shinya Yamanaka Nature, Volume: 474, Pages: 225-229, Date published: 09 June 2011, DOI: 10.1038/nature10106
    1. 転写因子Ｇｌｉｓ１により安全なｉＰＳ細胞の高効率作製に成功 平成２３年６月９日 京都大学 ｉＰＳ細胞研究所（ＣｉＲＡ） 転写因子Ｇｌｉｓ１の導入によりマウス／ヒトｉＰＳ細胞の樹立効率が大幅に改善される。Ｇｌｉｓ１は、不完全に初期化された細胞の増殖を抑制し、完全に初期化されたｉＰＳ細胞のみを増殖促進させる。
  2. Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008;26:101–106. doi: 10.1038/nbt1374.
  3. Wernig M, Meissner A, Cassady JP, Jaenisch R. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell. 2008;2:10–12. doi: 10.1016/j.stem.2007.12.001.

Other papers

  1. Tapia, N., MacCarthy, C., Esch, D. et al. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci Rep 5, 13533 (2015). https://doi.org/10.1038/srep13533

再生医療

幹細胞治療

  1. 42.5 : Stem Cell Therapy for Tissue Regeneration JoVE (1:21) 有料ライセンスが必要

心臓の再生医療

  1. Can we regenerate heart muscle with stem cells? | Chuck Murry TED チャンネル登録者数 2400万人 (14:35)
  2. Reverse engineering the human heart with pluripotent stem cells Labroots チャンネル登録者数 3.24万人　心臓オルガノイドを構築するアプローチ

遺伝子治療

  1. 15.10 : Gene Therapy JoVE 有料ライセンスが必要

organoid

  1. Differentiation of human iPSCs into lung organoids (27:07) The McDonnell Genome Institute, WashU Medicine チャンネル登録者数 132人

生殖工学

動物のクローニング

  1. Chapter 42.8 : Cloning of Dolly the Sheep JoVE (1:08) 有料ライセンスが必要

 

心臓の発生、血管の発生、循環器系の発生

心臓や血管は循環器系という閉じた管のネットワークを形成していますが、この複雑なネットワークはどのうようにして発生したのでしょうか。

何もないところから血管が形成されるvasculogenesis、すでに存在する血管からあらたな分岐や伸長が生じるangiogenesisという２つに大別されます。心臓の形成、動脈の形成などは、何もないところから管構造が生じるのが始まりです。

  1. https://obgynkey.com/cardiovascular-system-2/ https://i0.wp.com/obgynkey.com/wp-content/uploads/2020/03/f013-001-9780323611541.jpg

心臓や循環器系は中胚葉の細胞から生じます。中胚葉は外胚葉が内部に潜り込んでできますので、心臓になることが予定されている細胞はすでに2胚葉の円盤の外胚葉の細胞で決まっていると思われます。

  1. https://www.sheaheart.com/embryologyoftheheart/　　

心臓になることが予定される領域は、左右２つの場所に現れます。その２つが真ん中で融合して一つになり、crescentの形を示します。

  1. https://www.researchgate.net/figure/An-overview-of-cardiac-development-Cardiac-development-progresses-from-the-specification_fig1_262679781　https://www.researchgate.net/profile/Kathryn-Hentges/publication/262679781/figure/fig1/AS:280315064012809@1443843727720/An-overview-of-cardiac-development-Cardiac-development-progresses-from-the-specification.png
  2. 3D Heart Tube Embryology – Myoepicardial mantle – Proepicardial organ – CVS Embryology MedicoVisual – Visual Medical Lectures チャンネル登録者数 4.81万人 https://www.youtube.com/watch?v=tcM7DOSoabI
  3. https://staff.um.edu.mt/acus1/Heart-a.htm

 

心臓の初期発生

  1. Molecular Regulation of Cardiomyocyte Differentiation Sharon L. Paige, Karolina Plonowska, Adele Xu and Sean M. Wu Originally published16 Jan 2015https://doi.org/10.1161/CIRCRESAHA.116.302752Circulation Research. 2015;116:341–353　

心筋分化とWNTシグナルのタイミング

  1. World J Stem Cells. Aug 26, 2023; 15(8): 821-841 Published online Aug 26, 2023. doi: 10.4252/wjsc.v15.i8.821 Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo Muneer R, Qazi REM, Fatima A, Ahmad W, Salim A, Dini L, Khan I. Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo. World J Stem Cells 2023; 15(8): 821-841 [PMID: 37700819 DOI: 10.4252/wjsc.v15.i8.821]　https://www.wjgnet.com/1948-0210/full/v15/i8/821.htm
  2. Fu, Wb., Wang, W.E. & Zeng, Cy. Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors. Acta Pharmacol Sin 40, 9–12 (2019). 　https://doi.org/10.1038/s41401-018-0060-4
  3. Wnt/β-Catenin Signaling during Cardiac Development and Repair　J. Cardiovasc. Dev. Dis. 2014, 1(1), 98-110; https://doi.org/10.3390/jcdd1010098　https://www.mdpi.com/2308-3425/1/1/98
  4. The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development Susanne Gessert and Michael Kühl Originally published23 Jul 2010　https://doi.org/10.1161/CIRCRESAHA.110.221531　Circulation Research. 2010;107:186–199　
  5. Eldad Tzahor, Wnt/β-Catenin Signaling and Cardiogenesis: Timing Does Matter, Developmental Cell, Volume 13, Issue 1, 2007, Pages 10-13, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2007.06.006.　the Wnt/β-catenin pathway plays distinct, even opposing, roles during various stages of cardiac development.　WNTシグナルは、心筋分化において、働くタイミングに応じてポジティブにもネガティブにも働く
  6. Biphasic role for Wnt/β-catenin signaling in cardiac specification in zebrafish and embryonic stem cells Shuichi Ueno, Gilbert Weidinger, Tomoaki Osugi, +5, and Charles E. Murry murry@u.washington.eduAuthors Info & Affiliations June 5, 2007 104 (23) 9685-9690 https://doi.org/10.1073/pnas.0702859104　Developmental studies indicate that the Wnt/β-catenin pathway negatively regulates cardiac differentiation, whereas studies with pluripotent embryonal carcinoma cells suggest that this pathway promotes cardiogenesis. This apparent contradiction led us to hypothesize that Wnt/β-catenin signaling acts biphasically, either promoting or inhibiting cardiogenesis depending on timing. 　WNTシグナルは、心筋分化において、働くタイミングに応じてポジティブにもネガティブにも働く
  7. Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors Chulan Kwon, Joshua Arnold, Edward C. Hsiao, +2, and Deepak Srivastava dsrivastava@gladstone.ucsf.eduAuthors Info & Affiliations Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved May 21, 2007 June 26, 2007 104 (26) 10894-10899 https://doi.org/10.1073/pnas.0704044104

心臓・血管の発生

勉強に役立つ文書。

  1. ここまで知っておきたい発生学：発生・形態形成の基礎知識 Review 特集「日本小児循環器学会第14回教育セミナー」 　白石 公1,2 1 国立循環器病研究センター教育推進部 2 国立循環器病研究センター小児循環器科 発行日：2018年9月1日　心臓発生学を理解することは，先天性心疾患の形態診断，心疾患の病態把握，合併病変の予測，内科的治療方針の決定，外科手術手技の決定，長期予後の予測において大変重要である．本稿では，先天性心疾患の発症のメカニズムを理解するための胎生期の心臓形態形成のアウトラインについて解説する．　臨床医にとって基礎となる古典的な心臓形態形成の流れを中心に，図示してわかりやすく示す．

動脈の発生

大動脈は、左心室から発して上向し、カーブを描いて（大動脈弓）、下降していきます（下降大動脈）。しかしこの大動脈の形成過程は、思いのほか複雑です。あまりにも変化が激しいので教科書を読んでもなかなか理解できないのではないでしょうか。下の動画が実に見事にこの七変化をみせる動脈の発生過程を説明してくれていました。

Aortic Arches – Embryology in 3 minutes Medical Snippet チャンネル登録者数 3.44万人

  1. Aortic Arches and Large Arteries: Introduction by Peter Ward, PhD https://app.lecturio.com/#/lecture/c/7332/44490
  2. Development of aortic arch arteries & development of vertebral artery easy humananatomy チャンネル登録者数 1.55万人 https://www.youtube.com/watch?v=pwRjEBabH8Y  ventral aortaとdorsal aortaの説明から入っています。

循環器系の発生：心臓や血管の形成、血球系細胞の分化

  1. Embryology | Development of the Heart ❤️ (1:12:49) Ninja Nerd 2,880,000
  2. Embryology | Development of Vascular System (1:05:21) Ninja Nerd
  3. Interventricular septum development | Embryology made easy (6:42) Medical Snippet 31,200
  4. Cardiac Development by L. McCabe OPENPediatrics 197,000 (:41)
  5. Byte Size Med
    1. Development of the Heart | The Heart Tube | Part 1/3 | Cardiac Looping | Cardiovascular Embryology (11:47) embryonic foldingが重要。lateral foldingによって形成。
    2. Development of the Atria | Atrial Septum | Development of the Heart | Part 2/3 | Cardiac Embryology (10:37)
    3. Development of the Ventricles | Spiral Septum | Development of the Heart | Part 3/3 | Embryology (8:41)
  6. Lecturio Medical Embryology Course (Peter Ward, PhD)(4無料動画)
    1. Development of Thoracic Region and Vasculature Early Development of the heart: Malformations & Overview (Youtube 9:27)
    2. Formation of the Right and Left Atria (9:45)
  7. LIFE IN THE WOMB DR ROSE チャンネル登録者数 14万人
    1. DEVELOPMENT OF THE HEART TUBE IN A NUTSHELL

 

論文

  1. Bjarke Jensen, Tobias Wang, Vincent M. Christoffels, Antoon F.M. Moorman, Evolution and development of the building plan of the vertebrate heart, Biochimica et Biophysica Acta (BBA) – Molecular Cell Research, Volume 1833, Issue 4, 2013, Pages 783-794, ISSN 0167-4889, https://doi.org/10.1016/j.bbamcr.2012.10.004. The heart of the earliest vertebrates, possibly represented by Amphioxus, was probably a contractile vessel where peristaltic movements provide the perfusion of the vasculature at low pressures.
  2. Optimal morphometric factors responsible for enhanced gas exchange in fish gills https://arxiv.org/abs/1805.07744 魚のエラの構造がわかりやすい図が掲載されている

遺伝と環境、多様性

 

Genetic diseases

  1. Nondisjunction: Chromosomal Disorders & Aneuploidies – Medical Genetics | Lecturio (8:43)  Lecturio Medical チャンネル登録者数 73.3万人　non-disjunction 染色体の不分離
  2. Chromosomal Abnormalities, Aneuploidy and Non-Disjunction (7:46) BOGObiology チャンネル登録者数 5.19万人
  3. Autosomes: Structural Abnormalities – Genetics | Lecturio (4:47) Lecturio Medical チャンネル登録者数 73.3万人
  4. Autosomal Recessive Inheritance and Disorders – Genetics | Lecturio (13:13) Lecturio Medical チャンネル登録者数 73.3万人
  5. Down Syndrome – Genetics | Lecturio (13:07) Lecturio Medical チャンネル登録者数 73.3万人
  6. Multifactorial Inheritance: Risk Assessment of Qualitative Traits – Genetics | Lecturio (4:26) Lecturio Medical チャンネル登録者数 73.3万人

Skin colors

 

IQ and genes

  1. Genetics and Intelligence Robert Plomin (13:14) Serious Science チャンネル登録者数 10万人
  2. How DNA Makes Us Who We Are | Robert Plomin | Talks at Google (54:23) Talks at Google チャンネル登録者数 225万人
  3. Do Our Genes or Environment Influence Our Intelligence? (14:33) Andrew Klavan チャンネル登録者数 57.2万人

中胚葉由来の器官の発生：筋、骨、腎

脊索の形成

Fate of the Primitive Streak, Teratomas, formation of the Notochord, Diastematomyelia, Chordoma, + Douglas Gillard, DC, Professor of Clinical Science チャンネル登録者数 6.49万人

中胚葉由来の器官の発生

  1. Embryology | Mesoderm (26:55) Ninja Nerd チャンネル登録者数 289万人 ①paraaxial mesoderm, ②intermediate mesoderm, ③lateral plate mesodermそれぞれが何になるかが丁寧に解説されています。最後に中胚葉由来の器官をMESODERMCELLSという頭文字にして暗記の仕方まで説明。
    1. Myeloid stem cells,
    2. Erythroid stem cells,
    3. Spleen,
    4. gOnads,
    5. Dermis,
    6. Entire trunk,
    7. Renal system（腎尿路系）,
    8. Meninges,
    9. Adrenal cortex,
    10. Lymphoid stem cells/Lymph nodes,
    11. Cardiac stem cells,
    12. Endothelium of blood vessels,
    13. Lining of body cavities,
    14. Limbs（体肢、四肢）,
    15. Smooth muscle of GIT (gastrointestinal tract).
  2. Dermatomes & Myotomes – Anatomy Series (12:14) Medicosis Perfectionalis チャンネル登録者数 109万人 中胚葉１：５７〜

Somite 体節

  1. Somite (Wikipedia) The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide into the dermatomes,  myotomes,  sclerotomes and syndetomes that give rise to the vertebrae of the vertebral column, rib cage, part of the occipital bone, skeletal muscle, cartilage, tendons, and skin (of the back).
  2. Somite patterns The Noted Anatomist チャンネル登録者数 55.6万人 (5:43)
  3. EMBRYOLOGY (VIII): Somitogenesis & Differentiation: Meet the Sclerotome, Myotome, Dermatome Douglas Gillard, DC, Professor of Clinical Science チャンネル登録者数 6.31万人 (49:43)
  4. Embryology: Somitogenesis: Turning Paraxial Mesoderm into Dermatome, Myotome, and Sclerotome Douglas Gillard, DC, Professor of Clinical Science チャンネル登録者数 6.31万人 (56:06)
  5. Somite Formation & 90min clock Crash Biology チャンネル登録者数 452人 (12:02) 体節を順に形成していくときの細胞シグナリング分子

myotomes 筋節

Myotomes The Noted Anatomist チャンネル登録者数 55.6万人 (11:53)

  1. Myotomes and Peripheral nerves The Noted Anatomist チャンネル登録者数 55.6万人 (9:26)
  2. Dermatomes and Cutaneous fields The Noted Anatomist チャンネル登録者数 55.6万人 (10:57) 筋肉を支配する運動神経と皮膚からの感覚を脊髄に伝える感覚神経とは場所的に関連するので、併せてここで学ぶほうが頭が整理されます。（発生学的な由来はとりあえずおいておいて）
  3. Myotome https://www.physio-pedia.com/Myotomes A myotome (greek: myo=muscle, tome = a section, volume) is defined as a group of muscles which is innervated by single spinal nerve root.

Dermatomes

  1. Dermatomes The Noted Anatomist チャンネル登録者数 55.6万人 (11:47)

Sclerotomes 硬節(こうせつ)

Sclerotomes 硬節(こうせつ)は、骨や結合組織をつくる部分です。

骨格系の発生

  1. Embryology | Development of Skeletal System Ninja Nerd 2.88M subscribers (49:24)

骨のでき方は２つに大別されます。一つは、「膜性」、もうひとつが「軟骨」を経由する「内軟骨性骨化」です。

  1. 【骨化】より…その一つは，まず軟骨芽細胞によって軟骨性の雛型が形成され，つぎにそれが骨芽細胞によってつくられる骨組織に置きかわるもので，こうしてできる骨を軟骨性骨，置換骨，一次骨などとよぶ。もう一つは軟骨の段階をへずに結合組織(多くは真皮)の中に骨芽細胞によって直接に骨の基質がつくりだされるもので，こうした骨を膜骨(膜性骨)，皮骨，付加骨，二次骨などという。前者のほとんどは軟骨魚類のもつ軟骨性の内骨格と相同とみられる歴史的由来の古い骨，後者は古生代の原始魚類の外骨格や二次的に現れた歴史の新しい骨である。…
  2. 内骨格か外骨格か？ カメ甲羅の起源の論争に決着　2013年7月18日 　独立行政法人理化学研究所　発生・再生科学総合研究センター 　頭蓋骨は、真皮層中に生じ、骨の周辺に筋肉を伴わない外骨格　アルマジロの装甲は外骨格由来の皮骨　カメの背側の甲羅（背甲）は肋骨や背骨に由来　私たちの骨格は、進化における内骨格と外骨格の「せめぎ合い」の過程で獲得されたと言える。
  3. 内軟骨性骨化（軟骨内骨化）　実験医学OnLine
  4. 膜性骨化　実験医学OnLine 脊椎動物にみられる2種類の骨形成の過程の1つで，未分化間葉系細胞が骨芽細胞に分化し，直接，間葉系組織の中に骨組織を形成する骨化様式．頭頂骨などの扁平な骨組織の発生過程で観察される．
  5. Osteogenesis (Bone Formation): Intramembranous Ossification (Nursing) by Jasmine Clark, PhD　Lecturio.com
  6. Osteogenesis (Bone Formation): Endochondral Ossification (Nursing) by Jasmine Clark, PhD　Lecturio.com
  7. 骨の運命は生まれる前から決まっていた！？ 骨の発生、成長に関わる重要なメカニズムを発見 2022年11月29日　長崎大学
  8. 骨になるか軟骨になるかを運命づけるメカニズム　2013年4月24日　東京大学　軟骨組織を覆う軟骨膜には、胎児の骨格が形成される過程において、骨と軟骨の両方に分化できる前駆細胞が存在し、将来の骨形成に寄与すると考えられています。発生学的には、軟骨膜細胞は骨組織の細胞源となるだけでなく、特定の遺伝子が働かなくなると軟骨組織を形成することが知られています。これら軟骨膜細胞の分化決定にはヘッジホッグやBMP（Bone Morphogenetic Protein、骨形成性タンパク質）など、様々な因子により制御されていることはわかっています
  9. 骨格系（総論）

心臓の発生

  1. 循環器系の発生　のページにまとめました。

腎臓の形成

  1. 泌尿器・生殖器系の発生　のページにまとめました。

 

外胚葉由来の器官の発生：表皮、脳神経系、眼

外胚葉由来の器官の発生

  1. Embryology | Ectoderm (24:03) Ninja Nerd チャンネル登録者数 288万人

表皮の発生

脳神経系の構造

  1. Introduction to Neuroanatomy – Learn the Basics – Neuroanatomy Playlist（３２：２６） Medicosis Perfectionalis チャンネル登録者数 109万人
  2. 2-Minute Neuroscience: Myelin Neuroscientifically Challenged チャンネル登録者数 52.8万人

脳神経系の発生

神経系はすべて外胚葉由来ですが、細かくみると、中枢神経系は神経管に由来します。一方、末梢神経系は神経堤細胞(neural crest cells)に由来します。

During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to neural crest cells, which migrate extensively throughout the embryo, contributing to the majority of neurons and all of the glia of the PNS. The rest of the neural plate invaginates to form the neural tube, which expands to form the brain and spinal cord.

From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate　Dev Biol. 2015 Feb 15; 398(2): 135–146.　PMCID: PMC4845735

  1. 2-Minute Neuroscience: Early Neural development (1:59) Neuroscientifically Challenged チャンネル登録者数 52.8万人
  2. Embryology of the Nervous System | Development of CNS & PNS (14:31) Medicosis Perfectionalis チャンネル登録者数 109万人 神経発生の解説が始まるのは5:04から　末梢神経系の神経細胞の軸索は、神経(nerve)と呼ばれます。
  3. General Embryology – Detailed Animation On Neurulation Medical Animations 167K subscribers (1:49)
  4. Embryology | Neurulation, Vesiculation, Neural Crest Cell Migration Ninja Nerd 2.88M subscribers (34:17)
  5. Embryology of the Nervous System | Development of CNS & PNS Medicosis Perfectionalis チャンネル登録者数 109万人 (14:31

 

神経誘導の講義動画は形態の変化を説明したものが多いですが、形態の変化を引き起こしていいるのは遺伝子によって巧妙に制御された分子シグナリングです。

別記事→　神経誘導の分子シグナリング

Generation of cortical neurons

Arnold Kriegstein (UCSF) 1: Outer Subventricular Zone Radial Glia Cells – Brain Development Science Communication Lab チャンネル登録者数 17.7万人

10:20- single-labelled subcortical cells time lapse imaging

11:43 “we were very lucky at UCSF to get donated tissue”

*Gestational age is measured in weeks, from the first day of the woman’s last menstrual cycle to the current date. https://medlineplus.gov/ency/article/002367.htm

  1. Arnold Kriegstein (UCSF) 1: Outer Subventricular Zone Radial Glia Cells – Brain Development (31:04) Science Communication Lab チャンネル登録者数 17.7万人 Lecture
  2. Arnold Kriegstein – Genomic insights into human brain development, evolution, and disease  (43:54) Columbia University’s Zuckerman Institute チャンネル登録者数 4620人 Lecture
  3. CARTA: Livesey-Primate Brain Development; Huttner-Neocortex Expansion; Kriegstein-Brain Expansion (58:27) University of California Television (UCTV) チャンネル登録者数 130万人

主要な原著論文

  1. David V. Hansen, Jan H. Lui, Philip R. L. Parker & Arnold R. Kriegstein. Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554–561 (2010). https://doi.org/10.1038/nature08845
  2. Stephen C. Noctor, Alexander C. Flint, Tamily A. Weissman, Ryan S. Dammerman & Arnold R. Kriegstein. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001). https://doi.org/10.1038/35055553 (全文は有料） It has been suggested that radial glia may be neuronal precursors, but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1–3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons.

眼の発生

retinotopic mapの形成

axon guidance

 

Sensitive period

Plasticity

  1. Rewiring the Brain: The Promise and Peril of Neuroplasticity (1:26:29) World Science Festival チャンネル登録者数 123万人

 

神経新生

成人の脳ではあらたに神経細胞（ニューロン）がつくられることはないと長い間信じられてきて医学部の学部教育でもそう教えられてきましたが、その常識は最近覆りました。脳の一部の領域ではニューロンが成人の脳でも作られていることが発見されたのです。ニューロンが新生する(neurogenesis)領域の一つが海馬で、もうひとつがsubventricular zone (SVZ)と呼ばれる領域です。

Adult neurogenesis, the process of creating new neurons, involves the coordinated division, migration, and differentiation of neural stem cells. This process is restricted to neurogenic niches located in two distinct areas of the brain: the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle, where new neurons are generated and then migrate to the olfactory bulb.

  • 1960s New neurons could be generated in the DG and SVZ of the adult brain in cat and rat models (Altman, 1962, 1963; Altman and Das, 1965)
  • 1989 Adult brain neurogenesis in songbirds (Nottebohm, 1989).
  • 1998 Neurogenesis in the adult human hippocampus (in the postmortem tissue of cancer patients) (Eriksson et al., Nat Med. 1998 Nov;4(11):1313-7. ).
  • 1999 Adult macaque monkeys neurogenesis ten times lower than that of rodents (Gould et al., 1999)
  • 2013 carbon dating techniques to determine that the human DG adds up to 700 neurons per day (Spalding et al., 2013)
    • Kheirbek MA, Hen R. (Radio)active neurogenesis in the human hippocampus. Cell. 2013 Jun 6;153(6):1183-4. doi: 10.1016/j.cell.2013.05.033. PMID: 23746833; PMCID: PMC4046854. (Author manuscript)
  • 2018 studies using carbon 14 can produce unreliable results and are prone to noise and contamination (Sorrells et al., 2018).

Hussain et al. Adult neurogenesis: a real hope or a delusion? Neural Regen Res. 2024 Jan;19(1):6-15. doi: 10.4103/1673-5374.375317. PMCID: PMC10479850.

  1. Adult Neurogenesis – Alfredo Quiñones-Hinojosa (Johns Hopkins/HHMI) (5:09) iBiology Techniques チャンネル登録者数 7.21万人

総説論文

  1. Adult Neurogenesis ScienceDirect
  2. Zhang et al. Neurogenesis in primates versus rodents and the value of non-human primate models. National Science Review, Volume 10, Issue 11, November 2023, nwad248, https://doi.org/10.1093/nsr/nwad248
  3. The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis Daniel A. Lim and Arturo Alvarez-Buylla Cold Spring Harb Perspect Biol. 2016 May; 8(5): a018820. doi: 10.1101/cshperspect.a018820 PMCID: PMC4852803

参考

  1. Adult Hippocampal Neurogenesis: Growing New Brain Cells as an Adult (8:52) Maria Conley MD チャンネル登録者数 5220人
  2. Stem cells and adult neurogenesis EuroGCT and EuroStemCell チャンネル登録者数 8220人
  3. You can grow new brain cells. Here’s how | Sandrine Thuret | TED TED チャンネル登録者数 2410万人

神経系の再生医療

  1. How can we repair damaged axons? Science Animated チャンネル登録者数 2.87万人
  2. Can we repair injured nerves? | Massimo Hilliard | TEDxUQ TEDx Talks チャンネル登録者数 4030万人

脳オルガノイド

Brain Organoids 101 Harvard Brain Science Initiative チャンネル登録者数 1980人

  1. Arnold Kriegstein (UCSF) 2: Cerebral Organoids: Models of Human Brain Disease and Evolution （32:57）Science Communication Lab チャンネル登録者数 17.7万人
  2. Brain Organoids 101 (1:12:56) Harvard Brain Science Initiative チャンネル登録者数 1980人
  3. Facilitating Cerebral Organoid Culture via Lateral Soft Light Illumination DOI : 10.3791/63989-v • 9:10 min • June 6th, 2022 JoVE
  4. Generation of Human Brain Organoids for Mitochondrial Disease Modeling DOI : 10.3791/62756-v • 8:09 min • June 21st, 2021 JoVE
  5. Three-Dimensional Motor Nerve Organoid Generation DOI : 10.3791/61544-v • 9:57 min • September 24th, 2020 JoVE

 

 

 

 

体軸形成、HOX遺伝子によるパターン形成

体軸の位置はHOX遺伝子群の組み合わせにより規定されます。

HOX遺伝子に関する講義動画

  1. Hox Genes: From Mammalian Development to Human Genetic Syndromes （41：49）Somos Valdecilla チャンネル登録者数 1.45万人

HOX遺伝子による位置決めのメカニズム

  1. Transcriptional Regulation and Implications for Controlling Hox Gene Expression Zainab Afzal and Robb Krumlauf　J Dev Biol. 2022 Mar; 10(1): 4. 2022 Jan 10. doi: 10.3390/jdb10010004 PMCID: PMC8788451 　　
  2. Genesis. 2019 Jul-Aug; 57(7-8): e23296. Published online 2019 Apr 25. doi: 10.1002/dvg.23296 PMCID: PMC6767176 PMID: 31021058 What are the roles of retinoids, other morphogens, and Hox genes in setting up the vertebrate body axis? Antony J. Durstoncorresponding author 1　
  3. Hox Genes in the Adult Skeleton: Novel Functions Beyond Embryonic Development　Dev Dyn. 2017 Apr; 246(4): 310–317. Published online 2017 Jan 27. doi: 10.1002/dvdy.24482 PMCID: PMC5508556 NIHMSID: NIHMS875514 PMID: 28026082

成体におけるHOX遺伝子

  1. Hox Genes in the Adult Skeleton: Novel Functions Beyond Embryonic Development　Dev Dyn. 2017 Apr; 246(4): 310–317. Published online 2017 Jan 27. doi: 10.1002/dvdy.24482 PMCID: PMC5508556 NIHMSID: NIHMS875514 PMID: 28026082　Continued regional expression of Hox genes in adult tissues has been suggested by several independent studies, largely by the characterization of cells in culture.
  2. HOX GENES: Seductive Science, Mysterious Mechanisms　Ulster Med J. 2006 Jan; 75(1): 23–31. PMCID: PMC1891803 PMID: 16457401 　They are expressed during embryonic development in a highly co-ordinated manner and continue to be expressed in virtually all tissues and organs throughout adult life.

成体におけるHO

HOX遺伝子群による体軸上の位置決定に関する論文（原著・総説）

  1. What are the roles of retinoids, other morphogens, and Hox genes in setting up the vertebrate body axis?　Genesis. 2019 Jul-Aug; 57(7-8): e23296. Published online 2019 Apr 25. doi: 10.1002/dvg.23296 PMCID: PMC6767176  the core patterning mechanism is timing: BMP‐anti BMP mediated time space translation that regulates Hox temporal and spatial collinearities and Hox‐Hox auto‐ and cross‐ regulation. The known anterior–posterior morphogens and signaling pathways––retinoids, FGF’s, Cdx, Wnts, Gdf11 and others––interact with this core mechanism at and after space–time defined “decision points,” leading to the separation of distinct axial domains.

参考：ショウジョウバエの発生学

  1. Online Developmental Biology: Introduction to Drosophila Jason Pellettieri チャンネル登録者数

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