Regulation of embryonic stem cell pluripotency by heat shock protein 90

Eric Bradley, Erhard Bieberich, Nahid F Mivechi, Dantera Tangpisuthipongsa, Guanghu Wang

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Deciphering the molecular basis of stem cell pluripotency is fundamental to the understanding of stem cell biology, early embryonic development, and to the clinical application of regenerative medicine. We report here that the molecular chaperone heat shock protein 90 (Hsp90) is essential for mouse embryonic stem cell (ESC) pluripotency through regulating multiple pluripotency factors, including Oct4, Nanog, and signal transducer and activator of transcription 3. Inhibition of Hsp90 by either 17-NAllylamino-17- demethoxygeldanamycin or miRNA led to ESC differentiation. Overexpression of Hsp90β partially rescued the phenotype; in particular, the levels of Oct4 and Nanog were restored. Notably, Hsp90 associated with Oct4 and Nanog in the same cellular complex and protected them from degradation by the ubiquitin proteasome pathway, suggesting that Oct4 and Nanog are potential novel Hsp90 client proteins. In addition, Hsp90 inhibition reduced the mRNA level of Oct4, but not that of Nanog, indicating that Hsp90 participates in Oct4 mRNA processing or maturation. Hsp90 inhibition also increased expression of some protein markers for mesodermal lineages, implying that Hsp90 suppresses mesodermal differentiation from ESCs. These findings support a new role for Hsp90 in maintaining ESC pluripotency by sustaining the level of multiple pluripotency factors, particularly Oct4 and Nanog.

Original languageEnglish (US)
Pages (from-to)1624-1633
Number of pages10
JournalStem Cells
Volume30
Issue number8
DOIs
StatePublished - Aug 1 2012

Fingerprint

HSP90 Heat-Shock Proteins
Embryonic Stem Cells
Stem Cells
STAT3 Transcription Factor
Messenger RNA
Molecular Chaperones
Regenerative Medicine
Proteasome Endopeptidase Complex
Ubiquitin
MicroRNAs
Embryonic Development
Cell Biology
Cell Differentiation
Proteins
Phenotype

Keywords

  • Embryonic stem cells
  • Hsp70/Hsp90-organizing protein
  • Hsp90
  • Mesoderm
  • Nanog
  • Oct4
  • Pluripotency

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Bradley, E., Bieberich, E., Mivechi, N. F., Tangpisuthipongsa, D., & Wang, G. (2012). Regulation of embryonic stem cell pluripotency by heat shock protein 90. Stem Cells, 30(8), 1624-1633. https://doi.org/10.1002/stem.1143

Regulation of embryonic stem cell pluripotency by heat shock protein 90. / Bradley, Eric; Bieberich, Erhard; Mivechi, Nahid F; Tangpisuthipongsa, Dantera; Wang, Guanghu.

In: Stem Cells, Vol. 30, No. 8, 01.08.2012, p. 1624-1633.

Research output: Contribution to journalArticle

Bradley, E, Bieberich, E, Mivechi, NF, Tangpisuthipongsa, D & Wang, G 2012, 'Regulation of embryonic stem cell pluripotency by heat shock protein 90', Stem Cells, vol. 30, no. 8, pp. 1624-1633. https://doi.org/10.1002/stem.1143
Bradley E, Bieberich E, Mivechi NF, Tangpisuthipongsa D, Wang G. Regulation of embryonic stem cell pluripotency by heat shock protein 90. Stem Cells. 2012 Aug 1;30(8):1624-1633. https://doi.org/10.1002/stem.1143
Bradley, Eric ; Bieberich, Erhard ; Mivechi, Nahid F ; Tangpisuthipongsa, Dantera ; Wang, Guanghu. / Regulation of embryonic stem cell pluripotency by heat shock protein 90. In: Stem Cells. 2012 ; Vol. 30, No. 8. pp. 1624-1633.
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