Identification of a novel subset of alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy.
Identification of a novel subset of alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy.
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DOI：
10.1183/13993003.04168-2020
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Bellusci S
中科院分区：
文献类型：
--
作者：
Ahmadvand N;Khosravi F;Lingampally A;Wasnick R;Vazquez-Armendariz AI;Carraro G;Heiner M;Rivetti S;Lv Y;Wilhelm J;Gunther A;Herold S;Al Alam D;Chen C;Minoo P;Zhang JS;Bellusci S
肺泡2型(AT2)细胞是异质细胞，该谱系中的AT2亚群具有干细胞特性。然而，在AT2谱系中是否存在静止的、未成熟的细胞在肺再生过程中被激活尚不清楚。SftpcCreERT2/+；tdTomatoflox/FLOX小鼠用于AT2细胞的标记，标记的亚群通过流式细胞仪、定量聚合酶链式反应、转座酶可及染色质测序(ATAC-SEQ)、基因阵列、肺切除和肺切片培养进行分析。分析了人肺的单细胞RNA测序(scRNA-seq)数据。在小鼠中，我们检测到两个不同的AT2亚群，低tdTomato水平(Tomlow)和高tdTomato水平(TomHigh)。Tomlow细胞表达较低水平的AT2分化标志物FGFR2b和ETV5，而TomHigh作为真正成熟的AT2细胞，其Sftpc、Sftpb、Sftpa1、FGFR2b和ETV5表达水平较高。ATAC-seq分析表明，Tomlow和TomHigh细胞构成了两个不同的细胞群体，在Tomlow群体中存在Sftpc、rosa26和细胞周期基因座的特异性沉默。与假手术组相比，肺切除后Tomlow细胞数量增加，但TomHigh细胞数量增加，且Tomlow细胞FGFR2b、ETV5、Sftpc、Ccnd1和CCND2表达上调。Tomlow细胞过度表达程序性细胞死亡1配体1(PD-L1)，这是一种免疫抑制膜受体配体，流式细胞术用来区分这两个亚群。在人类肺中，对最近的scRNA-seq AT2数据集的数据挖掘证明了PD-L1Pos群体的存在。因此，我们在小鼠中发现了一个新的AT2静止的未成熟祖细胞群体，可以在肺切除后扩张，我们也为人类中存在这样的细胞提供了证据。一个新的AT2祖细胞群体已被鉴定为富含PD-L1。这种正常静止的AT2细胞亚群在肺泡损伤后高度增殖，并分化为成熟的AT2细胞。Https://bit.ly/31G0IIW
Alveolar type 2 (AT2) cells are heterogeneous cells, with specialised AT2 subpopulations within this lineage exhibiting stem cell properties. However, the existence of quiescent, immature cells within the AT2 lineage that are activated during lung regeneration is unknown. SftpcCreERT2/+;tdTomatoflox/flox mice were used for the labelling of AT2 cells and labelled subpopulations were analysed by flow cytometry, quantitative PCR, assay for transposase-accessible chromatin using sequencing (ATAC-seq), gene arrays, pneumonectomy and culture of precision-cut lung slices. Single-cell RNA-sequencing (scRNA-seq) data from human lungs were analysed. In mice, we detected two distinct AT2 subpopulations, with low tdTomato level (TomLow) and high tdTomato level (TomHigh). TomLow cells express lower levels of the AT2 differentiation markers Fgfr2b and Etv5, while TomHigh, as bona fide mature AT2 cells, show higher levels of Sftpc, Sftpb, Sftpa1, Fgfr2b and Etv5 expression. ATAC-seq analysis indicates that TomLow and TomHigh cells constitute two distinct cell populations, with specific silencing of Sftpc, Rosa26 and cell cycle gene loci in the TomLow population. Upon pneumonectomy, the number of TomLow but not TomHigh cells increases and TomLow cells show upregulated expression of Fgfr2b, Etv5, Sftpc, Ccnd1 and Ccnd2 compared to Sham. TomLow cells overexpress programmed cell death 1 ligand 1 (PD-L1), an immune inhibitory membrane receptor ligand, which is used by flow cytometry to differentially isolate these two subpopulations. In the human lung, data mining of a recent scRNA-seq AT2 data set demonstrates the existence of a PD-L1Pos population. Therefore, we have identified a novel population of AT2 quiescent, immature progenitor cells in mouse that expand upon pneumonectomy and we have provided evidence for the existence of such cells in human. A novel population of AT2 progenitor cells enriched for PD-L1 has been identified. This normally quiescent subpopulation of AT2 cells becomes highly proliferative and differentiates into mature AT2 in response to alveolar injury. https://bit.ly/31G0IIW
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影响因子：
23.9
作者：
Lechner AJ;Driver IH;Lee J;Conroy CM;Nagle A;Locksley RM;Rock JR
通讯作者：
Rock JR
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：
64.8
作者：
Zacharias WJ;Frank DB;Zepp JA;Morley MP;Alkhaleel FA;Kong J;Zhou S;Cantu E;Morrisey EE
通讯作者：
Morrisey EE
DOI：
10.1152/ajplung.00159.2003
发表时间：
2004-04-01
影响因子：
4.9
作者：
Reddy, R;Buckley, S;Driscoll, B
通讯作者：
Driscoll, B
影响因子：
5.6
作者：
Pawelczyk, Konrad;Piotrowska, Aleksandra;Nowinska, Katarzyna
通讯作者：
Nowinska, Katarzyna