SATB homeobox proteins regulate trophoblast stem cell renewal and differentiation

Kazuo Asanoma, Kaiyu Kubota, Damayanti Chakraborty, Stephen J. Renaud, Norio Wake, Kotaro Fukushima, Michael J. Soares, M. A.Karim Rumi

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34 Citations (Scopus)

Abstract

The morphogenesis of the hemochorial placenta is dependent upon the precise expansion and differentiation of trophoblast stem (TS) cells. SATB homeobox 1 (SATB1) and SATB2 are related proteins that have been implicated as regulators of some stem cell populations. SATB1 is highly expressed in TS cells, which prompted an investigation of SATB1 and the related SATB2 as regulators of TS cells. SATB1 and SATB2 were highly expressed in rat TS cells maintained in the stem state and rapidly declined following induction of differentiation. SATB proteins were also present within the rat placenta during early stages of its morphogenesis and disappeared as gestation advanced. Silencing Satb1 or Satb2 expression decreased TS cell self-renewal and increased differentiation, whereas ectopic expression of SATB proteins promoted TS cell expansion and blunted differentiation. Eomes, a key transcriptional regulator of TS cells, was identified as a target for SATB proteins. SATB knockdown decreased Eomes transcript levels and promoter activity, whereas SATB ectopic expression increased Eomes transcript levels and promoter activity. Electrophoretic mobility shift assay as well as chromatin immunoprecipitation analyses demonstrated that SATB proteins physically associate with a regulatory site within the Eomes promoter. We conclude that SATB proteins promote TS cell renewal and inhibit differentiation. These actions are mediated in part by regulating the expression of the TS cell stem-associated transcription factor, EOMES.

Original languageEnglish
Pages (from-to)2257-2268
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number3
DOIs
Publication statusPublished - Jan 13 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Asanoma, K., Kubota, K., Chakraborty, D., Renaud, S. J., Wake, N., Fukushima, K., Soares, M. J., & Rumi, M. A. K. (2012). SATB homeobox proteins regulate trophoblast stem cell renewal and differentiation. Journal of Biological Chemistry, 287(3), 2257-2268. https://doi.org/10.1074/jbc.M111.287128