Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations.
Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations.
复制标题
DOI：
10.1016/j.stem.2015.01.002
复制
发表时间：
2015-02-05
期刊：
影响因子：
23.9
通讯作者：
Rajagopal, Jayaraj
中科院分区：
文献类型：
--
作者：
Pardo-Saganta, Ana;Law, Brandon M.;Tata, Purushothama Rao;Villoria, Jorge;Saez, Borja;Mou, Hongmei;Zhao, Rui;Rajagopal, Jayaraj
损伤后，干细胞通过产生适当数量和比例的分化细胞来恢复正常的组织结构。目前的气道上皮再生模型提出，不同的细胞角蛋白8表达祖细胞，从p63+基底干细胞，随后分化成分泌和纤毛细胞谱系。我们现在表明，损伤后立即，离散的亚群p63+气道基底干/祖细胞本身表达Notch通路的成分与分泌或纤毛细胞的命运承诺。一个基底细胞群显示胞内Notch 2激活并直接产生分泌细胞;另一个表达c-myb并直接产生纤毛细胞。此外，破坏基底细胞群内的Notch配体活性通常会破坏谱系分离的正常模式。这些非细胞自主效应表明，有效的气道上皮再生需要更广泛的基底干/祖细胞群内的细胞间通讯。这些发现对于理解上皮再生和干细胞异质性具有广泛的意义。
Following injury, stem cells restore normal tissue architecture by producing the proper number and proportions of differentiated cells. Current models of airway epithelial regeneration propose that distinct cytokeratin 8-expressing progenitor cells, arising from p63+ basal stem cells, subsequently differentiate into secretory and ciliated cell lineages. We now show that immediately following injury, discrete subpopulations of p63+ airway basal stem/progenitor cells themselves express Notch pathway components associated with either secretory or ciliated cell fate commitment. One basal cell population displays intracellular Notch2 activation and directly generates secretory cells; the other expresses c-myb and directly yields ciliated cells. Furthermore, disrupting Notch ligand activity within the basal cell population at large disrupts the normal pattern of lineage segregation. These non-cell autonomous effects demonstrate that effective airway epithelial regeneration requires intercellular communication within the broader basal stem/progenitor cell population. These findings have broad implications for understanding epithelial regeneration and stem cell heterogeneity.
登录
查看更多内容
影响因子：
3.7
作者：
Koo BK;Yoon MJ;Yoon KJ;Im SK;Kim YY;Kim CH;Suh PG;Jan YN;Kong YY
通讯作者：
Kong YY
影响因子：
6.5
作者：
Diamond, I;Owolabi, T;Glick, A
通讯作者：
Glick, A
影响因子：
5.2
作者：
Pan, Jie-Hong;Adair-Kirk, Tracy L.;Patel, Anand C.;Huang, Tao;Yozamp, Nicholas S.;Xu, Jian;Reddy, E. Premkumar;Byers, Derek E.;Pierce, Richard A.;Holtzman, Michael J.;Brody, Steven L.
通讯作者：
Brody, Steven L.
DOI：
10.1165/rcmb.2013-0049oc
发表时间：
2013-12-01
影响因子：
6.4
作者：
Ghosh, Moumita;Ahmad, Shama;Reynolds, Susan D.
通讯作者：
Reynolds, Susan D.
影响因子：
30.5
作者：
Tanigakik, K;Han, H;Honjo, T
通讯作者：
Honjo, T