Prepubertal vulvovaginitis January 2018Journal of Nature and Science of Medicine 2(1) DOI:10.4103/JNSM.JNSM_33_18 License CC BY-NC-SA The majority of cases are due to nonspecific vulvovaginitis in which vaginal cultures will grow organisms considered to be part of the normal flora. The condition is easily managed with good perineal hygiene. In reluctant cases, oral antibiotics or local estrogen cream may be helpful.
The OSNA (One-Step Nucleic Acid Amplification) assay is a RT-PCR-based technique for detecting CK19 mRNA. It is a quantitative, fast, and standardised assay, and it has been validated for lymph node molecular analysis in breast and CRC [11,12,13].
A novel technique for pathological examination, OSNA, uses the reverse transcription loop-mediated isothermal amplification method to amplify CK19 mRNA.
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
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/)
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
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
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.
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.
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
Unique functions of Sonic hedgehog signaling during external genitalia
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
Mortlock, D., Innis, J. Mutation of HOXA13 in hand-foot-genital syndrome . Nat Genet15, 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.
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.
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.
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
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.
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/Klf4without c-Myc [4]. Although these iPS cells showed reduced tumorigenicity in chimeras and progeny mice, the reprogramming process is much slower, and efficiency is substantially reduced.
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 [1,5,9,10,15,16].
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
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
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.
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
Tapia, N., MacCarthy, C., Esch, D. et al. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci Rep5, 13533 (2015). https://doi.org/10.1038/srep13533
