COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.
Toni Marie DeloreyCarly G K ZieglerGraham HeimbergRachelly NormandYiming YangÅsa SegerstolpeDomenic AbbondanzaStephen J FlemingAyshwarya SubramanianDaniel T MontoroKarthik A JagadeeshKushal K DeyPritha SenMichal SlyperYered H Pita-JuárezDevan PhillipsJana BiermannZohar Bloom-AckermannNikolaos BarkasAndrea GannaJames GomezJohannes C MelmsIgor KatsyvErica NormandinPourya NaderiYury V PopovSiddharth S RajuSebastian NiezenLinus T-Y TsaiKatherine J SiddleMalika SudVictoria M TranShamsudheen K VellarikkalYiping WangLiat Amir-ZilbersteinDeepak S AtriJoseph BeechemOlga R BrookJonathan ChenPrajan DivakarPhylicia DorceusJesse M EngreitzAdam EsseneDonna M FitzgeraldRobin FropfSteven GazalJoshua GouldJohn GrzybTyler HarveyJonathan HechtTyler HetherJudit Jané-ValbuenaMichael Leney-GreeneHui MaCristin McCabeDaniel E McLoughlinEric M MillerChristoph MuusMari NiemiRobert PaderaLiuliu PanDeepti PantCarmel Pe'erJenna Pfiffner-BorgesChristopher J PintoJacob PlaistedJason ReevesMarty RossMelissa RudyErroll H RueckertMichelle SicilianoAlexander SturmEllen TodresAvinash WaghraySarah WarrenShuting ZhangDaniel R ZollingerLisa CosimiRajat M GuptaNir HacohenHanina HibshooshWinston HideAlkes L PriceJayaraj RajagopalPurushothama Rao TataStefan RiedelGyongyi SzaboTimothy L TicklePatrick T EllinorDeborah HungPardis C SabetiRichard NovakRobert RogersDonald E IngberZ Gordon JiangDejan JuricMehrtash BabadiSamouil L FarhiBenjamin IzarJames R StoneIoannis S VlachosIsaac H SolomonOrr AshenbergCaroline B M PorterBo LiAlex K ShalekAlexandra-Chloé VillaniOrit Rozenblatt-RosenAviv RegevPublished in: Nature (2021)
COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- single cell
- coronavirus disease
- acute respiratory distress syndrome
- heart failure
- stem cells
- genome wide
- gene expression
- early onset
- public health
- extracorporeal membrane oxygenation
- endothelial cells
- bone marrow
- atrial fibrillation
- peripheral blood
- mechanical ventilation
- cell proliferation
- signaling pathway
- oxidative stress
- kidney transplantation
- nucleic acid
- heat stress
- genome wide identification