Development and regeneration of Sox2+ endoderm progenitors are regulated by a Hdac1/2-Bmp4/Rb1 regulatory pathway.
Dev Cell, 2013/2/25;24(4):345-58.
Wang Y[1], Tian Y, Morley MP, Lu MM, Demayo FJ, Olson EN, Morrisey EE
Affiliations
PMID: 23449471
Impact factor: 13.417
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.
MeSH terms
Animals; Biomarkers; Blotting, Western; Bone Morphogenetic Protein 4; Cell Differentiation; Embryo, Mammalian; Endoderm; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hedgehog Proteins; Histone Deacetylase 1; Histone Deacetylase 2; Lung; Mice; Mice, Knockout; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Real-Time Polymerase Chain Reaction; Regeneration; Retinoblastoma Protein; Reverse Transcriptase Polymerase Chain Reaction; SOXB1 Transcription Factors; Stem Cells
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