Development and regeneration of Sox2+ Endoderm progenitors are regulated by a HDAC1/2-Bmp4/Rb1 regulatory pathway

Yi Wang, Ying Tian, Michael P. Morley, Min M. Lu, Francesco J. DeMayo, Eric N. Olson, Edward E. Morrisey

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

The mechanisms that govern the maintenance and differentiation of tissue-specific progenitors in development and tissue regeneration are poorly understood. We show that development of Sox2+ progenitors in the lung endoderm is regulated by histone deacetylases 1 and 2 (Hdac1/2). Hdac1/2 deficiency leads to a loss of Sox2 expression and a block in proximal airway development. This is mediated in part by derepression of Bmp4 and the tumor suppressor Rb1, which are direct transcriptional targets of Hdac1/2. In contrast to development, postnatal loss of Hdac1/2 in airway epithelium does not affect the expression of Sox2 or Bmp4. However, postnatal loss of Hdac1/2 leads to increased expression of the cell-cycle regulators Rb1, p21/Cdkn1a, and p16/Ink4a, resulting in a loss of cell-cycle progression and defective regeneration of Sox2+ lung epithelium. Thus, Hdac1/2 have both common and unique targets that differentially regulate tissue-specific progenitor activity during development and regeneration.

Original languageEnglish (US)
Pages (from-to)345-358
Number of pages14
JournalDevelopmental Cell
Volume24
Issue number4
DOIs
StatePublished - Feb 25 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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