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Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation

The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cell...

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Autores principales: Kee, Kehkooi, Angeles, Vanessa T, Flores, Martha, Nguyen, Ha Nam, Pera, Renee A Reijo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133736/
https://www.ncbi.nlm.nih.gov/pubmed/19865085
http://dx.doi.org/10.1038/nature08562
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author Kee, Kehkooi
Angeles, Vanessa T
Flores, Martha
Nguyen, Ha Nam
Pera, Renee A Reijo
author_facet Kee, Kehkooi
Angeles, Vanessa T
Flores, Martha
Nguyen, Ha Nam
Pera, Renee A Reijo
author_sort Kee, Kehkooi
collection PubMed
description The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.
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spelling pubmed-31337362011-07-12 Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation Kee, Kehkooi Angeles, Vanessa T Flores, Martha Nguyen, Ha Nam Pera, Renee A Reijo Nature Article The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications. 2009-10-28 2009-11-12 /pmc/articles/PMC3133736/ /pubmed/19865085 http://dx.doi.org/10.1038/nature08562 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kee, Kehkooi
Angeles, Vanessa T
Flores, Martha
Nguyen, Ha Nam
Pera, Renee A Reijo
Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation
title Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation
title_full Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation
title_fullStr Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation
title_full_unstemmed Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation
title_short Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation
title_sort human dazl, daz and boule genes modulate primordial germ cell and haploid gamete formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133736/
https://www.ncbi.nlm.nih.gov/pubmed/19865085
http://dx.doi.org/10.1038/nature08562
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