Single-cell analysis identified lung progenitor cells in COVID-19 patients.
Single-cell analysis identified lung progenitor cells in COVID-19 patients.
复制标题
单细胞分析鉴定出 COVID-19 患者的肺祖细胞
DOI：
10.1111/cpr.12931
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发表时间：
2020-12
影响因子：
8.5
通讯作者：
Zuo W
中科院分区：
文献类型：
--
作者：
Zhao Z;Zhao Y;Zhou Y;Wang X;Zhang T;Zuo W
The high mortality of severe 2019 novel coronavirus disease (COVID‐19) cases is mainly caused by acute respiratory distress syndrome (ARDS), which is characterized by increased permeability of the alveolar epithelial barriers, pulmonary oedema and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process. We focused on crucial roles of lung progenitor cells in alveolar cell regeneration and epithelial barrier re‐establishment and aimed to uncover a possible mechanism of lung repair after severe SARS‐CoV‐2 infection. Bronchoalveolar lavage fluid (BALF) of COVID‐19 patients was analysed by single‐cell RNA‐sequencing (scRNA‐seq). Transplantation of a single KRT5+ cell‐derived cell population into damaged mouse lung and time‐course scRNA‐seq analysis was performed. In severe (or critical) COVID‐19 patients, there is a remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar cell regeneration and epithelial barrier re‐establishment, respectively. The transplanted KRT5+ progenitors could long‐term engraft into host lung and differentiate into HOPX+ OCLN+ alveolar barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. This work uncovered the mechanism by which various lung progenitor cells work in concert to prevent and replenish alveoli loss post‐severe SARS‐CoV‐2 infection. The high mortality of severe 2019 novel coronavirus disease (COVID‐19) cases is mainly caused by acute respiratory distress syndrome (ARDS), which is characterized by increased permeability of the alveolar epithelial barriers, pulmonary oedema and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process. Here, by analysing the bronchoalveolar lavage fluid (BALF) of COVID‐19 patients through single cell RNA‐sequencing (scRNA‐Seq), we found that in severe (or critical) cases, there is remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar cell regeneration and epithelial barrier re‐establishment, respectively. In order to understand the function of KRT5+ progenitors in vivo, we transplanted a single KRT5+ cell‐derived cell population into damaged mouse lung. Time‐course single‐cell transcriptomic analysis showed that the transplanted KRT5+ progenitors could long‐term engraft into host lung and differentiate into HOPX+ OCLN+ alveolar barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. Similar barrier cells were also identified in some COVID‐19 patients with massive leukocyte infiltration. Altogether, this work uncovered the mechanism by which various lung progenitor cells work in concert to prevent and replenish alveoli loss post severe SARS‐CoV‐2 infection
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影响因子：
64.5
作者：
Kumar PA;Hu Y;Yamamoto Y;Hoe NB;Wei TS;Mu D;Sun Y;Joo LS;Dagher R;Zielonka EM;Wang de Y;Lim B;Chow VT;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
谱系阴性祖细胞大受伤后动员肺上皮。
影响因子：
64.8
作者：
Vaughan, Andrew E.;Brumwell, Alexis N.;Xi, Ying;Gotts, Jeffrey E.;Brownfield, Doug G.;Treutlein, Barbara;Tan, Kevin;Tan, Victor;Liu, Feng Chun;Looney, Mark R.;Matthay, Michael A.;Rock, Jason R.;Chapman, Harold A.
通讯作者：
Chapman, Harold A.
影响因子：
21.3
作者：
Xi Y;Kim T;Brumwell AN;Driver IH;Wei Y;Tan V;Jackson JR;Xu J;Lee DK;Gotts JE;Matthay MA;Shannon JM;Chapman HA;Vaughan AE
通讯作者：
Vaughan AE
DOI：
10.1183/13993003.02441-2018
发表时间：
2019-08
期刊：
The European respiratory journal
影响因子：
--
作者：
Morse C;Tabib T;Sembrat J;Buschur KL;Bittar HT;Valenzi E;Jiang Y;Kass DJ;Gibson K;Chen W;Mora A;Benos PV;Rojas M;Lafyatis R
通讯作者：
Lafyatis R
影响因子：
11.8
作者：
Yang Y;Riccio P;Schotsaert M;Mori M;Lu J;Lee DK;García-Sastre A;Xu J;Cardoso WV
通讯作者：
Cardoso WV