Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition
- PMID: 24989326
- DOI: 10.1002/stem.1781
Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition
Abstract
Primordial germ cells (PGCs) are embryonic germ cell precursors. Specification of PGCs occurs under the influence of mesodermal induction signaling during in vivo gastrulation. Although bone morphogenetic proteins and Wnt signaling play pivotal roles in both mesodermal and PGC specification, the signal regulating PGC specification remains unknown. Coculture of mouse embryonic stem cells (ESCs) with OP9 feeder cells induces mesodermal differentiation in vitro. Using this mesodermal differentiation system, we demonstrated that PGC-like cells were efficiently induced from mouse ESCs by extracellular signal-regulated kinase (ERK) signaling inhibition. Inhibition of ERK signaling by a MAPK/ERK kinase (MEK) inhibitor upregulated germ cell marker genes but downregulated mesodermal genes. In addition, the PGC-like cells showed downregulation of DNA methylation and formed pluripotent stem cell colonies upon treatment with retinoic acid. These results show that inhibition of ERK signaling suppresses mesodermal differentiation but activates germline differentiation program in this mesodermal differentiation system. Our findings provide a new insight into the signaling networks regulating PGC specification.
Keywords: ERK signal; Embryonic stem cells; In vitro differentiation; Mesoderm; Primordial germ cells.
© 2014 AlphaMed Press.
Similar articles
-
Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation.Biochem Biophys Res Commun. 2010 Feb 12;392(3):311-6. doi: 10.1016/j.bbrc.2010.01.005. Epub 2010 Jan 6. Biochem Biophys Res Commun. 2010. PMID: 20059970
-
A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants.Dev Cell. 2013 Dec 9;27(5):516-29. doi: 10.1016/j.devcel.2013.11.001. Dev Cell. 2013. PMID: 24331926
-
Pluripotent stem cells derived from mouse primordial germ cells by small molecule compounds.Stem Cells. 2015 Jan;33(1):45-55. doi: 10.1002/stem.1838. Stem Cells. 2015. PMID: 25186651
-
Induction of pluripotency in primordial germ cells.Histol Histopathol. 2011 May;26(5):643-50. doi: 10.14670/HH-26.643. Histol Histopathol. 2011. PMID: 21432780 Review.
-
In or out stemness: comparing growth factor signalling in mouse embryonic stem cells and primordial germ cells.Curr Stem Cell Res Ther. 2009 May;4(2):87-97. doi: 10.2174/157488809788167391. Curr Stem Cell Res Ther. 2009. PMID: 19442193 Review.
Cited by
-
Restoring Genetic Resource through In Vitro Culturing Testicular Cells from the Cryo-Preserved Tissue of the American Shad (Alosa sapidissima).Biology (Basel). 2022 May 22;11(5):790. doi: 10.3390/biology11050790. Biology (Basel). 2022. PMID: 35625518 Free PMC article.
-
Modulation of adhesion microenvironment using mesh substrates triggers self-organization and primordial germ cell-like differentiation in mouse ES cells.APL Bioeng. 2019 Mar 22;3(1):016102. doi: 10.1063/1.5072761. eCollection 2019 Mar. APL Bioeng. 2019. PMID: 31069335 Free PMC article.
-
2i Maintains a Naive Ground State in ESCs through Two Distinct Epigenetic Mechanisms.Stem Cell Reports. 2017 May 9;8(5):1312-1328. doi: 10.1016/j.stemcr.2017.04.001. Epub 2017 Apr 27. Stem Cell Reports. 2017. PMID: 28457889 Free PMC article.
-
Human pluripotent stem cell-derived DDX4 and KRT-8 positive cells participate in ovarian follicle-like structure formation.iScience. 2020 Dec 29;24(1):102003. doi: 10.1016/j.isci.2020.102003. eCollection 2021 Jan 22. iScience. 2020. PMID: 33490911 Free PMC article.
-
Germline specification from pluripotent stem cells.Stem Cell Res Ther. 2022 Feb 21;13(1):74. doi: 10.1186/s13287-022-02750-1. Stem Cell Res Ther. 2022. PMID: 35189957 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
