Review of Single-Cell RNA Sequencing in the Heart
Abstract
:1. Introduction
2. scRNA-seq Platforms
2.1. Platforms for Small Cells
2.2. Platforms for Large Cells
3. scRNA-seq and Cardiovascular Development and Disease
3.1. Murine Embryonic and Neonatal Heart
3.2. Murine Adult Heart
3.3. Human-Induced Pluripotent Stem Cells
3.4. Human Heart
4. scRNA-seq and Applications
4.1. Cell–Cell Interactions
4.2. Spatial Transcriptomes
4.3. Trajectory Analysis
5. Future Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
scRNA-seq | single-cell RNA sequencing |
CMs | cardiomyocytes |
IFC | integrated fluidic circuit |
FACS | fluorescence-activated cell sorting |
snRNA-seq | single-nucleus RNA-seq |
MI | myocardial infarction |
LAD | the left anterior descending artery |
I/R | ischemia/reperfusion |
TAC | transverse aortic constriction |
hiPSCs | human induced pluripotent stem cells |
seqFISH | sequential fluorescence in situ hybridization |
CODEX | Co-Detection by Indexing |
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Species | Vivo / Vitro | Age | Cells or Nuclei | Model | Device | Number of Cells for Analysis | Findings | Ref. |
---|---|---|---|---|---|---|---|---|
mouse | vivo | fetus | cells from whole heart | healthy development | IFC system | 2233 cells | chamber-specific genes in the embryonic mouse heart | [8] |
fetus | cells from whole heart | healthy development and Hand2 knock out | Chromium | 73,926 cells | Hand2 is a specifier of outflow tract cells | [12] | ||
fetus | cells from whole heart | healthy development and Hand2os1 knock out | Chromium | 3600 cells | lncRNA Hand2os1/Uph regulates Hand2 | [13] | ||
fetus | cells from whole heart and other 7 organs | healthy development | mouth pipette | 1819 cells | mutual interactions between epithelial and mesenchymal cells | [11] | ||
fetus | Mesp1 positive or null cardiac progenitors | healthy development and Mesp1 knock out | FACS | 598cells | Mesp1 is required for the exit from the pluripotent state | [10] | ||
fetus | Nkx2.5 or Isl1 expressing cardiac progenitors | healthy development | FACS | 1231 cells | Cxcr2 regulates chemotaxis during development | [9] | ||
fetus | cells from cardiac conduction system | healthy development | Chromium | 22,462 cells | transcriptional profiles of cardiac conduction system | [15] | ||
fetus | cells from cardiac outflow tract | healthy development | Chromium | 55,611cells | cellular transitions in cardiac outflow tract | [17] | ||
fetus ~ neonate | cells from whole heart | healthy development | IFC system | >1200 cells | temporal and chamber-specific markers during development | [7] | ||
neonate | nuclei from whole heart | healthy development and pediatric mitochondrial cardiomyopathy | Chromium | 15,083 nuclei | heterogeneity of various cell types | [14] | ||
neonate | cells from left ventricles | healthy development | ICELL8 | 4231 cells | transcriptomes of mono- or multi-nucleated cardiomyocytes are highly similar | [18] | ||
neonate ~ juvenile | cells from aortic valve and mitral valve | healthy development | Drop-seq | 2840 cells | Interstitial cell subpopulations undergo changes in gene expression during development | [16] | ||
neonate, adult | cells from ventricles | healthy, I/R and MI | FACS | 1939 cells | Cycling CMs are few adult mouse | [19] | ||
mouse | vivo | adult | cells from whole heart | healthy condition and ischemia reperfusion | FACS | 935 cells | Ckap4 is a modulator of fibroblasts activation | [6] |
adult | cells from whole heart | healthy and TAC | ICELL8 | 11,492 cells | Macrophage activation is a key factor of hypertrophy | [20] | ||
adult | cells from left ventricles | healthy development | ICELL8 | 2497 cells | Fibroblast regulates CM maturation | [21] | ||
adult | CMs from ventricles | healthy and TAC | ICELL 8 | <1015 cells | heterogeneity among CMs after TAC | [18] | ||
adult | CMs from whole heart | healthy and TAC | manual pickup | 396 cells | p53 induces molecular and morphological remodeling | [22] | ||
adult | nuclei from whole heart | healthy aging | Chromium | 27,808 nuclei | heterogeneity of fibroblasts with aging | [23] | ||
adult | nuclei from ventricles | healthy and MI | Chromium | 31,542 nuclei | dedifferentiation in cycling CMs after MI | [24] | ||
adult | nuclei of CMs from left ventricles | healthy and TAC | IFC system | 243 nuclei | lincRNA regulates dedifferentiation and cell cycle genes | [25] | ||
adult | cells from sinus node | healthy pacemaking | Chromium | 5357 nuclei | Membrane clock underpins pacemaking | [26] | ||
adult | non-CMs | healthy and MI | Chromium | 13,331 cells | transcriptome changes of non-CMs after MI | [27] | ||
adult | fibroblasts | healthy and MI | IFC system | 104 cells | transcriptome changes of fibroblast after MI | [27] | ||
adult | endothelial cells | healthy and MI | Chromium | 28,598 cells | Plvap regulates endothelial proliferation | [28] | ||
neonate, adult | neonatal CMs, and neonatal and adult fibroblasts | healthy development | ICELL8 | 1580 cells | Fibroblast regulates CM maturation | [21] | ||
human | vitro | hiPSC-CMs | differentiation | Chromium | 43,168 cells | Hopx is a key regulator of CM maturation | [29] | |
hiPSC-CMs | differentiation | Chromium | 10,376 cells | ISL1, NR2F2, TBX5, HEY2, or HOPX are makers of hiPSC-CMs | [30] | |||
hiPSC-CMs | differentiation | IFC system | 43 cells | ISL1, NR2F2, TBX5, HEY2, or HOPX are makers of hiPSC-CMs | [30] | |||
CMs derived from embryonic stem cells | differentiation | FACS | 366 cells | LGR5 is a marker of cardiac progenitors in embryonic outflow tract | [31] | |||
hiPSC-CMs | differentiation | Drop-seq | 23,554 cells | the comparison with DroNc-seq | [32] | |||
nuclei of hiPSC-CMs | differentiation | DroNc-seq | 24,318 nuclei | Inclusion of reads from intronic regions increases the sensitivity | [32] | |||
epicardium hiPSC-CMs | differentiation | FACS | 232 cells | BNC1 regulates cell heterogeneity | [33] | |||
CMs reprogrammed from human fibroblasts | differentiation | IFC system | 704 cells | cell fate transitions during reprogramming | [34] | |||
human | vivo | fetus | cells from free wall | healthy development | mouth pipette | 3842 cells | Atrial and ventricular CMs acquires distinct features early in heart development | [35] |
fetus | cells from whole heart | healthy development | Chromium | 4026 cells | cell atlas of the developing human heart | [36] | ||
fetus | cells from whole heart | healthy development | FACS | 458 cells | LGR5 is a marker of cardiac progenitors in embryonic outflow tract | [31] | ||
fetus | cells from whole heart | healthy and autoimmune-associated congenital heart block | Chromium | 17,747 cells | heterogeneous interferon responses in congenital heart block heart | [37] | ||
adult | cells from whole heart | healthy, HF and functional recovery from HF after treatment with LVAD | ICELL8 | 21,422 cells | CM contractility and metabolism are prominent aspects that are correlated with changes in heart function. | [38] | ||
adult | CMs from left ventricles | healthy and DCM | manual pickup | 411 cells | heterogeneity in DCM CMs | [22] | ||
adult | nuclei from whole heart | healthy | DroNuc-seq | 1491 nuclei | the usefulness of DroNc-seq in adult human CMs | [32] | ||
adult | nuclei from CMs | healthy and DCM | IFC system | 116 nuclei | lincRNA regulates dedifferentiation and cell cycle genes | [25] |
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Yamada, S.; Nomura, S. Review of Single-Cell RNA Sequencing in the Heart. Int. J. Mol. Sci. 2020, 21, 8345. https://doi.org/10.3390/ijms21218345
Yamada S, Nomura S. Review of Single-Cell RNA Sequencing in the Heart. International Journal of Molecular Sciences. 2020; 21(21):8345. https://doi.org/10.3390/ijms21218345
Chicago/Turabian StyleYamada, Shintaro, and Seitaro Nomura. 2020. "Review of Single-Cell RNA Sequencing in the Heart" International Journal of Molecular Sciences 21, no. 21: 8345. https://doi.org/10.3390/ijms21218345