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Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells

Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic sys...

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Autores principales: Panula, Sarita, Medrano, Jose V., Kee, Kehkooi, Bergström, Rosita, Nguyen, Ha Nam, Byers, Blake, Wilson, Kitchener D., Wu, Joseph C., Simon, Carlos, Hovatta, Outi, Reijo Pera, Renee A.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024045/
https://www.ncbi.nlm.nih.gov/pubmed/21131292
http://dx.doi.org/10.1093/hmg/ddq520
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author Panula, Sarita
Medrano, Jose V.
Kee, Kehkooi
Bergström, Rosita
Nguyen, Ha Nam
Byers, Blake
Wilson, Kitchener D.
Wu, Joseph C.
Simon, Carlos
Hovatta, Outi
Reijo Pera, Renee A.
author_facet Panula, Sarita
Medrano, Jose V.
Kee, Kehkooi
Bergström, Rosita
Nguyen, Ha Nam
Byers, Blake
Wilson, Kitchener D.
Wu, Joseph C.
Simon, Carlos
Hovatta, Outi
Reijo Pera, Renee A.
author_sort Panula, Sarita
collection PubMed
description Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications.
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spelling pubmed-30240452011-01-21 Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells Panula, Sarita Medrano, Jose V. Kee, Kehkooi Bergström, Rosita Nguyen, Ha Nam Byers, Blake Wilson, Kitchener D. Wu, Joseph C. Simon, Carlos Hovatta, Outi Reijo Pera, Renee A. Hum Mol Genet Articles Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications. Oxford University Press 2011-02-15 2010-12-03 /pmc/articles/PMC3024045/ /pubmed/21131292 http://dx.doi.org/10.1093/hmg/ddq520 Text en © The Author 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Panula, Sarita
Medrano, Jose V.
Kee, Kehkooi
Bergström, Rosita
Nguyen, Ha Nam
Byers, Blake
Wilson, Kitchener D.
Wu, Joseph C.
Simon, Carlos
Hovatta, Outi
Reijo Pera, Renee A.
Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
title Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
title_full Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
title_fullStr Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
title_full_unstemmed Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
title_short Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
title_sort human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024045/
https://www.ncbi.nlm.nih.gov/pubmed/21131292
http://dx.doi.org/10.1093/hmg/ddq520
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