Open AccessTBX3 Promotes Human Embryonic Stem Cell Proliferation and Neuroepithelial Differentiation in a Differentiation Stage‐dependent Manner
Author(s) -
Esmailpour Taraneh,
Huang Taosheng
Publication year - 2012
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.1187
Subject(s) - biology , embryonic stem cell , neuroepithelial cell , endoderm , microbiology and biotechnology , neuroectoderm , cellular differentiation , gene knockdown , pax6 , stem cell , ectoderm , neural stem cell , genetics , embryo , embryogenesis , mesoderm , transcription factor , gene
T‐box 3 (Tbx3) is a member of the T‐box family of genes. Mutations that result in the haploinsufficiency of TBX3 cause ulnar mammary syndrome in humans characterized by mammary gland hypoplasia as well as other congenital defects. In mice, homozygous mutations are embryonic lethal, suggesting that Tbx3 is essential for embryo development. Studies in mice have shown that Tbx3 is essential in the maintenance of mouse embryonic stem cell (ESC) self‐renewal and in their differentiation into extraembryonic endoderm (ExEn). The role TBX3 plays in regulating human ESCs (hESCs) has not been explored. Since mouse and hESCs are known to represent distinct pluripotent states, it is important to address the role of TBX3 in hESC self‐renewal and differentiation. Using overexpression and knockdown strategies, we found that TBX3 overexpression promotes hESC proliferation possibly by repressing the expression of both NFκBIB and p14 ARF , known cell cycle regulators. During differentiation, TBX3 knockdown resulted in decreased neural rosette formation and in decreased expression of neuroepithelial and neuroectoderm markers ( PAX6 , LHX2 , FOXG1 , and RAX ). Taken together, our data suggest a role for TBX3 in hESC proliferation and reveal an unrecognized novel role of TBX3 in promoting neuroepithelial differentiation. Our results suggest that TBX3 plays distinct roles in regulating self‐renewal and differentiation in both hESCs and mouse ESCs. S TEM C ells 2012;30:2152–2163