Acute loss of Cited2 impairs Nanog expression and decreases self-renewal of mouse embryonic stem cells.
Identifying novel players of the pluripotency gene regulatory network centered on Oct4, Sox2, and Nanog as well as delineating the interactions within the complex network is key to understanding self-renewal and early cell fate commitment of embryonic stem cells (ESC). While overexpression of the transcriptional regulator Cited2 sustains ESC pluripotency, its role in ESC functions remains unclear. Here, we show that Cited2 is important for proliferation, survival, and self-renewal of mouse ESC. We position Cited2 within the pluripotency gene regulatory network by defining Nanog, Tbx3, and Klf4 as its direct targets. We also demonstrate that the defects caused by Cited2 depletion are, at least in part, rescued by Nanog constitutive expression. Finally, we demonstrate that Cited2 is required for and enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Kamil R
KR
Kranc
Daniel V
DV
Oliveira
Alejandro
A
Armesilla-Diaz
Ivette
I
Pacheco-Leyva
Ana
A
Catarina Matias
Ana
A
Luisa Escapa
Chithra
C
Subramani
Helen
H
Wheadon
Marlene
M
Trindade
Jennifer
J
Nichols
Keisuke
K
Kaji
Tariq
T
Enver
José
J
Bragança
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C486381:CITED2 protein, human; C110087:Cited2 protein, mouse; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators
Cited2; Nanog; Pluripotency; Self-renewal; Transcriptional regulation