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_G.H23,304 cells mm_donors_A.B22,495 cells mm_donors_I.J22,336 cells mm_donors_C.D21,301 cells mm_donors_E.F18,406 cells mm_donors_KK.LL5,929 cells mm_donors_II.JJ4,584 cells mm_donors_BB.CC4,164 cells mm_donors_OO.PP3,406 cells mm_donors_MM.NN1,847 cells mm_donors_EE.FF1,352 cells mm_donors_GG.HH1,077 cells myocardial infarction (MI)98,446 cells type B pancreatic cell21,129 cells endothelial cell16,991 cells kidney tubule cell10,138 cells dendritic cell4,954 cells pancreatic A cell4,122 cells pancreatic D cell2,698 cells natural killer cell2,158 cells pancreatic PP cell995 cells hepatic stellate cell787 cells endocardial cell737 cells mature NK T cell167 cells cardiac muscle cell105 cells 10–12 weeks old194,315 cells blood_sham_d30_run118,277 cells blood_sham_d01_run116,470 cells blood_MI_d01_run115,144 cells blood_MI_d30_run114,784 cells blood_MI_d07_run213,479 cells blood_sham_d07_run212,679 cells heart_MI_d07_run29,825 cells heart_MI_d01_run28,846 cells heart_sham_d01_run28,145 cells islets_MI_d01_run16,157 cells islets_sham_d01_run16,025 cells kidney_MI_d07_run45,929 cells islets_MI_d07_run15,815 cells heart_sham_d07_run25,727 cells islets_sham_d30_run15,545 cells kidney_sham_d07_run44,584 cells islets_MI_d30_run14,419 cells liver_sham_d07_run34,164 cells islets_sham_d07_run14,106 cells heart_sham_d30_run34,059 cells liver_MI_d01_run33,847 cells kidney_MI_d30_run43,406 cells liver_sham_d01_run32,889 cells liver_MI_d07_run32,872 cells heart_MI_d30_run32,846 cells kidney_sham_d30_run41,847 cells liver_sham_d30_run21,352 cells liver_MI_d30_run21,077 cells Blood 30dpi SH18,277 cells Blood 1dpi SH16,470 cells Blood 1dpi MI15,144 cells Blood 30dpi MI14,784 cells Blood 7dpi MI13,479 cells Blood 7dpi SH12,679 cells Heart 1dpi, MI8,846 cells Pancreatic Islets 1dpi MI6,157 cells Pancreatic Islets 1dpi SH6,025 cells Kidney 7dpi MI5,929 cells Pancreatic Islets 7dpi MI5,815 cells Pancreatic Islets 30dpi SH5,545 cells Kidney 7dpi SH4,584 cells Pancreatic Islets 30dpi MI4,419 cells Pancreatic Islets 7dpi SH4,106 cells Heart 30dpi SH4,059 cells Kidney 30dpi SH3,406 cells Heart 30dpi MI2,846 cells Kidney 30dpi MI1,847 cells Liver 30dpi SH1,352 cells Liver 30dpi MI1,077 cells Pancreatic Islets32,067 cells Pancreatic Islets32,067 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 stage70,783 cells zf_WKM_injury_dpi79,608 cells zf_WKM_injury_dpi18,344 cells zf_WKM_ctrl_ctrl7,379 cells zf_Liver_ctrl_ctrl7,163 cells zf_Pancreas_ctrl_ctrl6,034 cells zf_Heart_injury_dpi15,613 cells zf_Pancreas_injury_dpi75,137 cells zf_Liver_injury_dpi75,097 cells zf_Pancreas_injury_dpi14,966 cells zf_Heart_injury_dpi74,475 cells zf_Heart_ctrl_ctrl3,613 cells zf_Liver_injury_dpi13,354 cells Pancreas_ctrl_dpictrl6,034 cells Pancreas_injury_dpi75,137 cells Pancreas_injury_dpi14,966 cells WKM 7 dpi replicate 25,494 cells Pancreas 7 dpi5,137 cells Pancreas 1 dpi4,966 cells WKM 1 dpi replicate 24,468 cells WKM 7 dpi replicate 14,114 cells WKM 1 dpi replicate 13,876 cells liver Ctrl replicate 23,771 cells WKM Ctrl replicate 23,713 cells WKM Ctrl replicate 13,666 cells liver Ctrl replicate 13,392 cells heart 1 dpi replicate 22,891 cells heart 7 dpi replicate 12,820 cells heart 1 dpi replicate 12,722 cells liver 7 dpi replicate 12,712 cells liver 7 dpi replicate 22,385 cells heart Ctrl replicate 21,827 cells heart Ctrl replicate 11,786 cells liver 1 dpi replicate 21,734 cells heart 7 dpi replicate 21,655 cells liver 1 dpi replicate 11,620 cells Whole Kidney Marrow25,331 cells Whole Kidney Marrow25,331 cells Whole Kidney Marrow25,331 cells Heart cryoinjury70,783 cells myeloid leukocyte10,709 cells pancreatic acinar cell7,336 cells hematopoietic stem cell3,409 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
