Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis (Cell, 2014, 156(3):440-455)

報告日期: 2014/11/18
報告時間: 4:00/4:50
報告學生: 謝妙禧
講評老師: 洪澤民
附件下載: 下載[1441-1412238201-1.pdf] 

 Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis

Lee, J. H., et al. Cell, 2014, 156(3):440-455 

Speaker: Miao-Hsi Hsieh  (謝妙禧)                             Commentator:Tse-Ming Hong (洪澤民老師)

Time: 16 :00~16:50, Nov. 18, 2014                           Place: Room 602 

Abstract:

The supporting cells and factors in specialized niches regulate properties of adult tissue stem cells, including self-renewal and differentiation (1). However, it is unclear how supporting cells or factors control regenerative potential, repair of lung and lineage-specific differentiation of lung stem cell. Bronchioalveolar stem cells (BASCs), adult murine distal lung epithelial stem cells, resided in the bronchioalveolar duct junction, where the airways open to the alveolar space (2). The authors used 3D coculture to mimic the niche microenvironment and asked whether the endothelial cell in the lung can support BASCs growth. The data showed that endothelial cells can support BASCs function, such as self-renew, and differentiate into three type colonies- bronchiolar colonies, alveolar colonies, and bronchioalveolar colonies. It indicated endothelial cells promoted multi-lineage differentiation of BASCs. In addition, BASCs coclutured with lung but not liver specific endothelial cells could dramatically increase alveolar cells differentiation and decrease bronchia differentiation. The finding suggested the BASC differentiation was an organ-specific manner. The authors further found that the BMP4-NFATc1-TSP1 signaling pathway in primary mouse lung endothelial cells (LuMECs) was required for specifically differentiation of BASCs to alveolar cells. Finally, the author used two lung injury mouse models to demonstrate that BMP4-NFATc1-TSP1 axis was critical for alveolar cell differentiation. In naphthalene induced lung Carla cells (bronchiolar cells) injury model, bronchiolar cells were increased in TSP1-/- mice compared to TSP1 wild type mice during repair, indicating that TSP1 promoted BASC differentiation to bronchia cells. Likewise, in bleomycin induced AT2 cells (alveolar cells) injury model, ablation of TSP1 gave rise to decrease AT2 cell population and repress BASCs differentiation. The data indicated that BASCs cannot differentiate to alveolar to repair lung damage that lead to more severely fibrosis in TSP1-/- mice compared to wild-type mice. Taken together, the authors defined the organ-specific BMP4-NFATc1-TSP1 axis in lung endothelial cells modulated lineage-specific lung stem cell differentiation that could be a therapeutic avenue for these and other numerous lung diseases.

References:

  1. D. Leanne Jones and Amy J. Wagers. No place like home: anatomy and function of the stem cell niche. Nat Rev Mol Cell Biol. 2008, 9(1):11-21.
  2. Carla F. Bender Kim, et al. Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer. Cell. 2005, 121(6):823-35.