Transcriptional responses to injury of regenerative lung alveolar epithelium.
Transcriptional responses to injury of regenerative lung alveolar epithelium.
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DOI：
10.1016/j.isci.2022.104843
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发表时间：
2022-08-19
期刊：
影响因子：
5.8
通讯作者：
Tian, Ying
中科院分区：
文献类型：
--
作者：
Ali, Mir;LaCanna, Ryan;Lian, Zhaorui;Huang, Jian;Tan, Yinfei;Shao, Wenna;Yu, Xiang;Tian, Ying
肺泡上皮2型(AT2)细胞的增殖对肺泡上皮细胞损伤后的动态平衡和再生的意义已被广泛接受。然而，AT2细胞群体对细胞增殖能力的异质性仍存在争议。通过单细胞RNA测序和Ki67基因敲入小鼠模型的遗传谱系标记，我们定位了肺炎链球菌感染诱导的小鼠肺内稳态和再生后所有增殖的AT2细胞。增殖的AT2细胞群体表现出独特的转录程序，该程序受激活转录因子3(ATF3)和甲状腺激素受体α(THRA)转录因子的调节。这两种转录因子在AT2细胞中的过表达促进了AT2细胞的增殖，改善了损伤后的肺功能。这些结果表明，在肺上皮再生开始时，ATF3和THRA的表达增加，以允许AT2细胞快速增殖，从而通过肺上皮的恢复而进展。小鼠肺泡上皮2型(AT2)细胞是异质性ScRNA-seq在增殖的AT2细胞中发现独特的转录程序ATF3和THRA因子在AT2细胞生物学；干细胞研究；Omics；转录组学中发挥增殖功能
The significance of alveolar epithelial type 2 (AT2) cell proliferation for lung alveolar epithelial homeostasis and regeneration after injury has been widely accepted. However, the heterogeneity of AT2 cell population for cell proliferation capacity remains disputed. By single-cell RNA sequencing and genetic lineage labeling using the Ki67 knock-in mouse model, we map all proliferative AT2 cells in homeostatic and regenerating murine lungs after injury induced by Streptococcus pneumoniae infection. The proliferative AT2 cell population displays a unique transcriptional program, which is regulated by activating transcription factor 3 (ATF3) and thyroid hormone receptor alpha (THRA) transcription factors. Overexpression of these two transcription factors in AT2 cells promoted AT2 cell proliferation and improved lung function after injury. These results indicate that increased expression of ATF3 and THRA at the onset of lung epithelial regeneration is required to permit rapid AT2 cell proliferation and hence progression through the recovery of lung epithelium. Alveolar epithelial type 2 (AT2) cells in mice are heterogeneous ScRNA-seq identified a unique transcriptional program in proliferative AT2 cells ATF3 and THRA factors exert proliferative functions in AT2 cells Cell biology; Stem cells research; Omics; Transcriptomics
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
Elf5 是胚胎肺上皮特异性的成纤维细胞生长因子敏感转录因子
影响因子：
2.5
作者：
Metzger, David E.;Xu, Yan;Shannon, John M.
通讯作者：
Shannon, John M.
影响因子：
2.7
作者：
Li, CG;Xiao, J;Minoo, P
通讯作者：
Minoo, P
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
15.9
作者：
LaCanna, Ryan;Liccardo, Daniela;Tian, Ying
通讯作者：
Tian, Ying