TBX3 Promotes Human Embryonic Stem Cell Proliferation and Neuroepithelial Differentiation in a Differentiation Stage-dependent Manner§

Authors

  • Taraneh Esmailpour,

    1. Department of Pediatrics, Division of Human Genetics, University of California, Irvine, California, USA
    2. Department of Pathology,University of California, Irvine, California, USA
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  • Taosheng Huang

    Corresponding author
    1. Department of Pediatrics, Division of Human Genetics, University of California, Irvine, California, USA
    2. Department of Pathology,University of California, Irvine, California, USA
    3. Department of Developmental and Cell Biology, University of California, Irvine, California, USA
    • Division of Genetics, Department of Pediatrics, 3113 Gillespie Neuroscience Research Facility, University of California, Irvine, California 92697, USA

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    • Telephone: 949-824-9346; Fax: 949-824-9776


  • Author contributions: T.E.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.H.: conception and design, financial support, provision of study material, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS August 2, 2012.

Abstract

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 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, 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. STEM Cells2012;30:2152–2163

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