PDCD2 is essential for inner cell mass development and embryonic stem cell maintenance.
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.
Mu
Weipeng
W
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Munroe
Robert J
RJ
Barker
Anna K
AK
Schimenti
John C
JC
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
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C484279:Pdcd2 protein, mouse; D034741:RNA, Small Interfering; D014212:Tretinoin
Development. 2010 Jan;137(1):27-31
20023157
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2860-5
11854457
Mamm Genome. 2005 Nov;16(11):838-46
16284799
Scand J Gastroenterol. 2004 May;39(5):464-9
15180185
Genes Dev. 2005 Jul 1;19(13):1581-95
15998811
Mol Cell Biol. 1998 Dec;18(12):7185-91
9819405
Nature. 2007 Nov 15;450(7168):415-9
17928865
J Biol Chem. 2002 Jul 19;277(29):26524-9
12011100
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10860-5
9724795
Genes Dev. 1997 Mar 15;11(6):726-37
9087427
Mol Cell Biol. 2005 Aug;25(16):6990-7004
16055712
Stem Cells. 2005 Oct;23(9):1343-56
16081666
Cell. 2008 Jun 27;133(7):1162-74
18585351
Genes Dev. 1998 Aug 1;12(15):2278-92
9694794
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7449-54
17468402
Mol Cell Biol. 2005 Oct;25(19):8507-19
16166633
Cell. 2005 Sep 23;122(6):947-56
16153702
Cytogenet Cell Genet. 1995;71(1):41-3
7606924
Oncogene. 1994 Mar;9(3):809-18
8108123
Oncogene. 2001 Jan 4;20(1):125-32
11244510
FEBS Lett. 1999 Sep 24;458(3):324-8
10570933
Nat Genet. 2002 May;31(1):25-32
11923873
Mol Cell Biol. 2008 Oct;28(20):6439-51
18710940
Genes Chromosomes Cancer. 2003 Aug;37(4):421-6
12800155
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
15075390
FEBS Lett. 2002 Aug 28;526(1-3):119-23
12208517
Annu Rev Biochem. 1996;65:801-47
8811196
Dev Biol. 2000 Sep 1;225(1):151-68
10964471
Mol Cell. 2007 Jul 6;27(1):107-19
17612494
Hum Mol Genet. 2008 Apr 15;17(R1):R28-36
18632693
Dev Biol. 2005 Jun 15;282(2):374-84
15950603
Nat Genet. 2006 Apr;38(4):431-40
16518401
J Cell Biol. 1990 Mar;110(3):569-80
2307700
Genetics. 2002 Feb;160(2):675-82
11861570
FEBS Lett. 2005 Jan 17;579(2):398-408
15642350
Mol Cell Biol. 1991 Aug;11(8):4177-88
2072913
Development. 2007 Jul;134(13):2387-96
17522156
Development. 2010 Feb;137(3):395-403
20081188
Genes Cells. 2005 Jul;10(7):717-31
15966902
Cell. 2000 Sep 15;102(6):753-63
11030619
Oncogene. 2002 Aug 8;21(34):5245-54
12149646
Nature. 2002 Oct 31;419(6910):934-9
12410313
Science. 2002 Oct 18;298(5593):597-600
12228720
Mol Cell Biol. 1992 May;12(5):2391-5
1569957
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4168-72
18332431
Science. 1996 Dec 6;274(5293):1672-7
8939849