Hedgehog-responsive PDGFRa(+) fibroblasts maintain a unique pool of alveolar epithelial progenitor cells during alveologenesis.
Hedgehog-responsive PDGFRa(+) fibroblasts maintain a unique pool of alveolar epithelial progenitor cells during alveologenesis.
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DOI：
10.1016/j.celrep.2022.110608
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发表时间：
2022-04-05
期刊：
影响因子：
8.8
通讯作者：
Minoo, Parviz
中科院分区：
文献类型：
--
作者：
Gao, Feng;Li, Changgong;Danopoulos, Soula;Al Alam, Denise;Peinado, Neil;Webster, Sha;Borok, Zea;Kohbodi, GoleNaz Adeli;Bellusci, Saverio;Minoo, Parviz
肺泡内衬有肺泡1型（AT 1）和2型（AT 2）上皮细胞。在肺泡发生过程中，与肺泡数量增加相关的需求增加通过增殖的祖细胞AT 2（pAT 2）来满足。关于这一群体的身份及其生态位微环境的信息很少。我们发现，在肺泡发生过程中，刺猬响应PDGFRa（+）祖细胞（也称为SCMF）是分泌营养分子的来源，维持独特的pAT2群体。SCMF又通过TGFβ信号传导维持。SCMF中Alk5 TβR2的复合失活减少了它们的数量，并耗尽了pAT 2库，而不影响子细胞的分化。在死于支气管肺发育不良的早产儿的肺中，PDGFRa减少，增殖性AT 2的数量减少，表明在肺泡发生期间进化上保守的机制支配PAT 2行为。SCMF是一个短暂的细胞群，仅在肺泡发生期间活跃，使其成为哺乳动物器官中独特的阶段特异性小生境中胚层细胞类型。许多关于肺中肺泡上皮细胞异质性的信息来自成年小鼠。Gao等分析了肺泡形成过程中肺泡上皮细胞群的复杂性，肺泡形成是新生儿慢性肺病支气管肺发育不良发病机制中中断的过程。
The lung alveolus is lined with alveolar type 1 (AT1) and type 2 (AT2) epithelial cells. During alveologenesis, increasing demand associated with expanding alveolar numbers is met by proliferating progenitor AT2s (pAT2). Little information exists regarding the identity of this population and their niche microenvironment. We show that during alveologenesis, Hedgehog-responsive PDGFRa(+) progenitors (also known as SCMFs) are a source of secreted trophic molecules that maintain a unique pAT2 population. SCMFs are in turn maintained by TGFβ signaling. Compound inactivation of Alk5 TβR2 in SCMFs reduced their numbers and depleted the pAT2 pool without impacting differentiation of daughter cells. In lungs of preterm infants who died with bronchopulmonary dysplasia, PDGFRa is reduced and the number of proliferative AT2s is diminished, indicating that an evolutionarily conserved mechanism governs pAT2 behavior during alveologenesis. SCMFs are a transient cell population, active only during alveologenesis, making them a unique stage-specific niche mesodermal cell type in mammalian organs. Much of the information regarding heterogeneity of alveolar epithelial cells in the lung is from adult mice. Gao et al. analyze the complexity of the alveolar epithelial cell population during alveologenesis, a process interrupted in the pathogenesis of the neonatal chronic lung disease bronchopulmonary dysplasia.
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影响因子：
64.8
作者：
De Simone A;Evanitsky MN;Hayden L;Cox BD;Wang J;Tornini VA;Ou J;Chao A;Poss KD;Di Talia S
通讯作者：
Di Talia S
影响因子：
5.2
作者：
Hu, Yan;Ng-Blichfeldt, John-Poul;Koenigshoff, Melanie
通讯作者：
Koenigshoff, Melanie
影响因子：
8
作者：
Frazier NM;Brand T;Gordan JD;Grandis J;Jura N
通讯作者：
Jura N
DOI：
10.1242/dev.163014
发表时间：
2018-05-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Chung MI;Bujnis M;Barkauskas CE;Kobayashi Y;Hogan BLM
通讯作者：
Hogan BLM
影响因子：
4
作者：
Clement MS;Gammelgaard KR;Nielsen AL;Sorensen BS
通讯作者：
Sorensen BS