title: PDCD2 is essential for inner cell mass development and embryonic stem cell maintenance.
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.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Mu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Munroe
authors.forename: Anna K
authors.initials: AK
authors.lastname: Barker
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
mesh_terms: D000483:Alleles; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D053624:Blastocyst Inner Cell Mass / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D014018:Tissue Distribution; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C484279:Pdcd2 protein, mouse; D034741:RNA, Small Interfering; D014212:Tretinoin
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