SATB Homeobox Proteins Regulate Trophoblast Stem Cell Renewal and Differentiation

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 cell...

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Bibliographic Details
Published in:The Journal of biological chemistry 2012-01, Vol.287 (3), p.2257-2268
Main Authors: Asanoma, Kazuo, Kubota, Kaiyu, Chakraborty, Damayanti, Renaud, Stephen J., Wake, Norio, Fukushima, Kotaro, Soares, Michael J., Rumi, M.A. Karim
Format: Article
Language:English
Subjects:
Animals
CDX2
Cell Differentiation - physiology
Cell Line
Development
Developmental Biology
Differentiation
EOMES
Female
Matrix Attachment Region Binding Proteins - genetics
Matrix Attachment Region Binding Proteins - metabolism
Placenta
Pregnancy - physiology
Pregnancy Proteins - genetics
Pregnancy Proteins - metabolism
Promoter Regions, Genetic - physiology
Rats
Rats, Sprague-Dawley
SATB Proteins
Stem Cells
Stem Cells - cytology
Stem Cells - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Trophoblast
Trophoblasts - cytology
Trophoblasts - metabolism
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Summary: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. Background: Trophoblast cells, the functional components of the placenta, are derived from multipotent trophoblast stem (TS) cells. Results: SATB homeobox proteins regulate the TS cell stem state through up-regulation of a stem-specific transcription factor, EOMES, and inhibition of trophoblast differentiation. Conclusion: SATB proteins regulate TS cell development. Significance: Understanding TS cell biology is crucial to determining processes underlying placental development.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.287128