TY - JOUR
T1 - Development and regeneration of Sox2+ Endoderm progenitors are regulated by a HDAC1/2-Bmp4/Rb1 regulatory pathway
AU - Wang, Yi
AU - Tian, Ying
AU - Morley, Michael P.
AU - Lu, Min M.
AU - DeMayo, Francesco J.
AU - Olson, Eric N.
AU - Morrisey, Edward E.
N1 - Funding Information:
The authors thank Brigid L. Hogan for sharing the Bmp4 flox mice. These studies were supported by funding from the National Institutes of Health to E.E.M. (HL071589, HL087825, HL100405, and HL110942) and an American Heart Association Predoctoral fellowship award to Y.W. (11PRE7580096).
PY - 2013/2/25
Y1 - 2013/2/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875344085&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2013.01.012
DO - 10.1016/j.devcel.2013.01.012
M3 - Article
C2 - 23449471
AN - SCOPUS:84875344085
SN - 1534-5807
VL - 24
SP - 345
EP - 358
JO - Developmental cell
JF - Developmental cell
IS - 4
ER -