TBX3 promotes human embryonic stem cell proliferation and neuroepithelial differentiation in a differentiation stage-dependent manner.
TBX3 promotes human embryonic stem cell proliferation and neuroepithelial differentiation in a differentiation stage-dependent manner.
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DOI：
10.1002/stem.1187
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发表时间：
2012-10
期刊：
影响因子：
5.2
通讯作者：
Huang, Taosheng
中科院分区：
文献类型：
--
作者：
Esmailpour, Taraneh;Huang, Taosheng
T-box 3(TBX3)是T-box基因家族中的一员。导致TBX3单倍性不足的突变会导致人类尺侧乳腺综合征(UMS)，特征是乳腺发育不全以及其他先天性缺陷。在小鼠中，纯合子突变对胚胎是致命的，这表明TBX3对胚胎发育是必不可少的。在小鼠身上的研究表明，TBX3在维持小鼠胚胎干细胞(ESC)的自我更新和分化为胚胎外内胚层(Exen)过程中是必不可少的。Tbx3在调节人类胚胎干细胞中的作用还没有被探索。由于已知小鼠和人类胚胎干细胞代表不同的多能状态，因此研究Tbx3在人类胚胎干细胞自我更新和分化中的作用是很重要的。采用过表达和敲除策略，我们发现Tbx3过表达可能通过抑制已知的细胞周期调节因子NFκbib和p14ARF的表达来促进人胚胎干细胞的增殖。在分化过程中，Tbx3基因敲除导致神经花环形成减少，神经上皮和神经外胚层标记物(PAX6、LHX2、FOXG1、RAX)表达减少。综上所述，我们的数据提示了TBX3在人类胚胎干细胞增殖中的作用，并揭示了TBX3在促进神经上皮细胞分化中的一个未知的新角色。我们的结果表明，TBX3在调节人和小鼠胚胎干细胞的自我更新和分化方面发挥着不同的作用。
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 (UMS) 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 extra-embryonic endoderm (ExEn). The role TBX3 plays in regulating human ESCs has not been explored. Since mouse and human ESCs are known to represent distinct pluripotent states, it is important to address the role of TBX3 in human ESC self-renewal and differentiation. Using over-expression and knockdown strategies, we found that TBX3 over-expression promotes human ESC proliferation possibly by repressing the expression of both NFκBIB and p14ARF, 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, RAX). Taken together, our data suggests a role for TBX3 in human ESC proliferation and reveals 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 human and mouse ESCs.
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影响因子：
2.7
作者：
Behesti, Hourinaz;Papaioannou, Virginia E.;Sowden, Jane C.
通讯作者：
Sowden, Jane C.
DOI：
10.1083/jcb.121.3.491
发表时间：
1993-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Itoh M;Nagafuchi A;Yonemura S;Kitani-Yasuda T;Tsukita S;Tsukita S
通讯作者：
Tsukita S
影响因子：
--
作者：
Behesti H;Holt JK;Sowden JC
通讯作者：
Sowden JC
DOI：
10.1073/pnas.1004584107
发表时间：
2010-05-18
影响因子：
11.1
作者：
Hanna, Jacob;Cheng, Albert W.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
11.2
作者：
Fan, WW;Huang, X;Huang, TS
通讯作者：
Huang, TS