PMID- 31915373 OWN - NLM STAT- MEDLINE DCOM- 20200423 LR - 20210731 IS - 1476-4679 (Electronic) IS - 1465-7392 (Linking) VI - 22 IP - 1 DP - 2020 Jan TI - Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function. PG - 108-119 LID - 10.1038/s41556-019-0446-7 [doi] AB - Owing to the prevalence and high mortality rates of cardiac diseases, a more detailed characterization of the human heart is necessary; however, this has been largely impeded by the cellular diversity of cardiac tissue and limited access to samples. Here, we show transcriptome profiling of 21,422 single cells-including cardiomyocytes (CMs) and non-CMs (NCMs)-from normal, failed and partially recovered (left ventricular assist device treatment) adult human hearts. Comparative analysis of atrial and ventricular cells revealed pronounced inter- and intracompartmental CM heterogeneity as well as compartment-specific utilization of NCM cell types as major cell-communication hubs. Systematic analysis of cellular compositions and cell-cell interaction networks showed that CM contractility and metabolism are the most prominent aspects that are correlated with changes in heart function. We also uncovered active engagement of NCMs in regulating the behaviour of CMs, exemplified by ACKR1(+)-endothelial cells, injection of which preserved cardiac function after injury. Beyond serving as a rich resource, our study provides insights into cell-type-targeted intervention of heart diseases. FAU - Wang, Li AU - Wang L AUID- ORCID: 0000-0002-5570-1336 AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. wangl@pumc.edu.cn. FAU - Yu, Peng AU - Yu P AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Zhou, Bingying AU - Zhou B AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Song, Jiangping AU - Song J AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Li, Zheng AU - Li Z AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Zhang, Mingzhi AU - Zhang M AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Guo, Guangran AU - Guo G AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Wang, Yin AU - Wang Y AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Chen, Xiao AU - Chen X AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Han, Leng AU - Han L AUID- ORCID: 0000-0002-7380-2640 AD - Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA. FAU - Hu, Shengshou AU - Hu S AUID- ORCID: 0000-0002-7473-6729 AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. huss@fuwaihospital.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200108 PL - England TA - Nat Cell Biol JT - Nature cell biology JID - 100890575 SB - IM MH - Cell Differentiation/physiology MH - Endothelial Cells/*metabolism MH - Gene Expression Profiling/methods MH - Heart Failure/*metabolism MH - Heart Ventricles/*metabolism MH - Humans MH - Myocytes, Cardiac/*metabolism EDAT- 2020/01/10 06:00 MHDA- 2020/04/24 06:00 CRDT- 2020/01/10 06:00 PHST- 2019/03/21 00:00 [received] PHST- 2019/11/28 00:00 [accepted] PHST- 2020/01/10 06:00 [entrez] PHST- 2020/01/10 06:00 [pubmed] PHST- 2020/04/24 06:00 [medline] AID - 10.1038/s41556-019-0446-7 [pii] AID - 10.1038/s41556-019-0446-7 [doi] PST - ppublish SO - Nat Cell Biol. 2020 Jan;22(1):108-119. doi: 10.1038/s41556-019-0446-7. Epub 2020 Jan 8.