Elsevier

Developmental Biology

Volume 347, Issue 2, 15 November 2010, Pages 279-288
Developmental Biology

PDCD2 is essential for inner cell mass development and embryonic stem cell maintenance

https://doi.org/10.1016/j.ydbio.2010.08.026Get rights and content
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Abstract

PDCD2 is a conserved eukaryotic protein implicated in cell cycle regulation by virtue of its interactions with HCFC1 and the NCOR1/SIN3A corepressor complex. Pdcd2 transcripts are enriched in ES cells and other somatic stem cells, and its ortholog is essential for hematopoietic stem cell maintenance in Drosophila. To characterize the physiological role(s) of mammalian PDCD2, we created a disruption allele in mice. Pdcd2−/− embryos underwent implantation but did not undergo further development. Inner cell masses (ICMs) from Pdcd2−/− blastocysts failed to outgrow in vitro. Furthermore, embryonic stem cells (ESCs) require PDCD2 as demonstrated by the inability to generate Pdcd2−/− ESCs in the absence of an ectopic transgene. Upon differentiation of ESCs by retinoic acid treatment or LIF deprivation, PDCD2 levels declined. In conjunction with prior studies, these results indicate that in vivo, PDCD2 is critical for blastomere and ESC maintenance by contributing to the regulation of genes in a manner essential to the undifferentiated state of these cells.

Abbreviations

ESC
embryonic stem cell
ICM
inner cell mass
RA
retinoic acid
MEF
mouse embryonic fibroblast
LIF
leukemia inhibitory factor

Keywords

Mouse development
Embryonic stem cells
Cell differentiation
Preimplantation

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1

Current address: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.