Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury
Cite
Cortada, E., Yao, J., Xia, Y., Dündar, F., Zumbo, P., Yang, B., Rubio-Navarro, A., Perder, B., Qiu, M., Pettinato, A.M. and Homan, E.A., 2024. Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury. Communications Biology, 7(1), pp.1-20. https://doi.org/10.1038/s42003-024-07315-x
Abstract
The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics. We interrogate the extracardiac reaction to cardiomyocyte necrosis to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages play a critical role in determining tissue homeostasis by healing versus scarring. We identify distinct transcriptional clusters of monocytes/macrophages (mono/Mϕ) in each species and find analogous pairs in zebrafish and mice. However, the reaction to myocardial injury is largely disparate between mice and zebrafish. The dichotomous response to heart damage between the murine and zebrafish mono/Mϕ and/or the presence of distinct zebrafish mono/Mϕ subtypes may underlie the impaired regenerative process in adult mammals and humans. Our study furnishes a direct cross-species comparison of immune responses between regenerative and profibrotic myocardial injury models, providing a useful resource to the fields of regenerative biology and cardiovascular research.
Datasets
Subject ID
Time point
Disease
Cell type
Assay
Sex
Age
Sample ID
Sample name
GEO accession
Sample source
Tissue
Genotype
Surgery
Mouse strand
Leiden clustering
mm_donors_KK.LL5929 cells mm_donors_II.JJ4584 cells mm_donors_BB.CC4164 cells mm_donors_OO.PP3406 cells mm_donors_MM.NN1847 cells mm_donors_EE.FF1352 cells mm_donors_GG.HH1077 cells myocardial infarction (MI)98446 cells type B pancreatic cell21129 cells endothelial cell16991 cells kidney tubule cell10138 cells pancreatic A cell4122 cells pancreatic D cell2698 cells natural killer cell2158 cells pancreatic PP cell995 cells hepatic stellate cell787 cells endocardial cell737 cells mature NK T cell167 cells cardiac muscle cell105 cells 10–12 weeks old194315 cells blood_sham_d30_run118277 cells blood_sham_d01_run116470 cells blood_MI_d01_run115144 cells blood_MI_d30_run114784 cells blood_MI_d07_run213479 cells blood_sham_d07_run212679 cells heart_MI_d07_run29825 cells heart_MI_d01_run28846 cells heart_sham_d01_run28145 cells islets_MI_d01_run16157 cells islets_sham_d01_run16025 cells kidney_MI_d07_run45929 cells islets_MI_d07_run15815 cells heart_sham_d07_run25727 cells islets_sham_d30_run15545 cells kidney_sham_d07_run44584 cells islets_MI_d30_run14419 cells liver_sham_d07_run34164 cells islets_sham_d07_run14106 cells heart_sham_d30_run34059 cells liver_MI_d01_run33847 cells kidney_MI_d30_run43406 cells liver_sham_d01_run32889 cells liver_MI_d07_run32872 cells heart_MI_d30_run32846 cells kidney_sham_d30_run41847 cells liver_sham_d30_run21352 cells liver_MI_d30_run21077 cells Blood 30dpi SH18277 cells Blood 30dpi MI14784 cells Pancreatic Islets 1dpi MI6157 cells Pancreatic Islets 1dpi SH6025 cells Pancreatic Islets 7dpi MI5815 cells Pancreatic Islets 30dpi SH5545 cells Pancreatic Islets 30dpi MI4419 cells Pancreatic Islets 7dpi SH4106 cells Kidney 30dpi SH3406 cells Kidney 30dpi MI1847 cells Pancreatic Islets32067 cells Pancreatic Islets32067 cells Assay
Development stage
Subject ID
cluster_k50
Post surgery
Sample ID
Sample name
GEO accession
Sample source
Tissue
Sample type
Genotype
Disease
Cell type
Leiden clustering
prime adult stage70783 cells zf_WKM_injury_dpi79608 cells zf_WKM_injury_dpi18344 cells zf_WKM_ctrl_ctrl7379 cells zf_Liver_ctrl_ctrl7163 cells zf_Pancreas_ctrl_ctrl6034 cells zf_Heart_injury_dpi15613 cells zf_Pancreas_injury_dpi75137 cells zf_Liver_injury_dpi75097 cells zf_Pancreas_injury_dpi14966 cells zf_Heart_injury_dpi74475 cells zf_Heart_ctrl_ctrl3613 cells zf_Liver_injury_dpi13354 cells Pancreas_ctrl_dpictrl6034 cells Pancreas_injury_dpi75137 cells Pancreas_injury_dpi14966 cells WKM 7 dpi replicate 25494 cells WKM 1 dpi replicate 24468 cells WKM 7 dpi replicate 14114 cells WKM 1 dpi replicate 13876 cells liver Ctrl replicate 23771 cells WKM Ctrl replicate 23713 cells WKM Ctrl replicate 13666 cells liver Ctrl replicate 13392 cells heart 1 dpi replicate 22891 cells heart 7 dpi replicate 12820 cells heart 1 dpi replicate 12722 cells liver 7 dpi replicate 12712 cells liver 7 dpi replicate 22385 cells heart Ctrl replicate 21827 cells heart Ctrl replicate 11786 cells liver 1 dpi replicate 21734 cells heart 7 dpi replicate 21655 cells liver 1 dpi replicate 11620 cells Whole Kidney Marrow25331 cells Whole Kidney Marrow25331 cells Whole Kidney Marrow25331 cells Heart cryoinjury70783 cells myeloid leukocyte10709 cells pancreatic acinar cell7336 cells hematopoietic stem cell3409 cells nucleated thrombocyte650 cells cardiac muscle cell615 cells Alias names
GSE227191, GSE227189, GSE227190, Single cell transcriptomic analyses of the dynamic local and systemic response to cardiac injury in mice and zebrafish
