Single-cell analysis reveals the function of lung progenitor cells in COVID-19 patients
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Abstract
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 edema 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 1 . Here by analyzing 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 engrafted 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 that how various lung progenitor cells work in concert to prevent and replenish alveoli loss post severe SARS-CoV-2 infection.
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SciScore for 10.1101/2020.07.13.200188: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All animals were cared for in accordance with NIH guidelines, and all animal experiments were performed under the guidance of the Institutional Animal Care and Use Committee of Tongji University. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Animal experiments: C57/B6 mice (6–8 weeks) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. (China) and housed in specific pathogen-free conditions within an animal care facility (Center of Laboratory Animal, Tongji University, Shanghai, China). C57/B6suggested: NoneSciScore for 10.1101/2020.07.13.200188: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All animals were cared for in accordance with NIH guidelines, and all animal experiments were performed under the guidance of the Institutional Animal Care and Use Committee of Tongji University. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Animal experiments: C57/B6 mice (6–8 weeks) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. (China) and housed in specific pathogen-free conditions within an animal care facility (Center of Laboratory Animal, Tongji University, Shanghai, China). C57/B6suggested: NoneSoftware and Algorithms Sentences Resources Epithelial cells were re-clustered with Seurat v.3. Seuratsuggested: (SEURAT, RRID:SCR_007322)Gene functional annotation: Gene Ontology (GO) enrichment analysis and Gene Set Enrichment Analysis (GSEA) of differentially expressed genes was implemented by the ClusterProfiler R package ClusterProfilersuggested: (clusterProfiler, RRID:SCR_016884)Single cell trajectory analysis: To construct single cell pseudotime trajectory and to identify genes that change as the cells undergo transition, Monocle2 (version 2.4.0) algorithm 26 was applied to our datasets. Monocle2suggested: (Monocle2, RRID:SCR_016339)Differences of gene expression levels between healthy controls, moderate and severe groups were compared using MAST in Seurat v.3. MASTsuggested: (MAST, RRID:SCR_016340)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 23. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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