title: SATB homeobox proteins regulate trophoblast stem cell renewal and differentiation.
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.
authors: Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors: Kazuo
authors: K
authors: Asanoma
authors: Kaiyu
authors: K
authors: Kubota
authors: Damayanti
authors: D
authors: Chakraborty
authors: Stephen J
authors: SJ
authors: Renaud
authors: Norio
authors: N
authors: Wake
authors: Kotaro
authors: K
authors: Fukushima
authors: Michael J
authors: MJ
authors: Soares
authors: M A Karim
authors: MA
authors: Rumi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005260:Female; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy / Q000502:physiology*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D011257:Pregnancy Proteins; D014157:Transcription Factors