Open AccessAcute Loss of C ited2 Impairs N anog Expression and Decreases Self‐Renewal of Mouse Embryonic Stem Cells
Author(s) -
Kranc Kamil R.,
Oliveira Daniel V.,
Armesilla-Diaz Alejandro,
Pacheco-Leyva Ivette,
Catarina Matias Ana,
Luisa Escapa Ana,
Subramani Chithra,
Wheadon Helen,
Trindade Marlene,
Nichols Jennifer,
Kaji Keisuke,
Enver Tariq,
Bragança José
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1889
Subject(s) - homeobox protein nanog , biology , sox2 , reprogramming , embryonic stem cell , induced pluripotent stem cell , klf4 , microbiology and biotechnology , rex1 , stem cell , nanog homeobox protein , genetics , gene
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. S tem C ells 2015;33:699–712