Cells of the adult human heart

Abstract

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.

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References 100

1. 1.

   Meilhac SM, Buckingham ME. The deployment of cell lineages that form the mammalian heart. Nat. Rev. Cardiol. 2018;15:705-724.

   Not in our library10.1038/s41569-018-0086-9

2. 2.

   Svensson V, Vento-Tormo R, Teichmann SA. Exponential scaling of single-cell RNA-seq in the past decade. Nat. Protocols. 2018;13:599-604.

   Not in our library10.1038/nprot.2017.149

3. 3.

   Wang L, et al. Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function. Nat. Cell Biol. 2020;22:108-119.

   Not in our library10.1038/s41556-019-0446-7

4. 4.

   Tucker NR, et al. Transcriptional and cellular diversity of the human heart. Circulation. 2020;142:466-482.

   Not in our library10.1161/circulationaha.119.045401

5. 5.

   Chung AK, et al. Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study. Circulation. 2006;113:1597-1604.

   Not in our library10.1161/circulationaha.105.574400

6. 6.

   Johnson EK, Matkovich SJ, Nerbonne JM. Regional differences in mRNA and lncRNA expression profiles in non-failing human atria and ventricles. Sci. Rep. 2018;8:13919.

   Not in our library10.1038/s41598-018-32154-2

7. 7.

   Delplancq G, et al. Cardiomyopathy due to PRDM16 mutation: first description of a fetal presentation, with possible modifier genes. Am. J. Med. Genet. C. Semin. Med. Genet. 2020;184:129-135.

   Not in our library10.1002/ajmg.c.31766

8. 8.

   Kim S-Y, Yasuda S, Tanaka H, Yamagata K, Kim H. Non-clustered protocadherin. Cell Adhes. Migr. 2011;5:97-105.

   Not in our library10.4161/cam.5.2.14374

9. 9.

   Donlin LT, et al. Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization. Genes Dev. 2012;26:114-119.

   Not in our library10.1101/gad.177758.111

10. 10.

    Mazzotta S, et al. Distinctive roles of canonical and noncanonical Wnt signaling in human embryonic cardiomyocyte development. Stem Cell Reports. 2016;7:764-776.

    Not in our library10.1016/j.stemcr.2016.08.008

11. 11.

    Shenton FC, Pyner S. Expression of transient receptor potential channels TRPC1 and TRPV4 in venoatrial endocardium of the rat heart. Neuroscience. 2014;267:195-204.

    Not in our library10.1016/j.neuroscience.2014.02.047

12. 12.

    Gao M, et al. Conserved expression of the PRELI domain containing 2 gene (Prelid2) during mid-later-gestation mouse embryogenesis. J. Mol. Histol. 2009;40:227-233.

    Not in our library10.1007/s10735-009-9234-1

13. 13.

    Putku M, et al. CDH13 promoter SNPs with pleiotropic effect on cardiometabolic parameters represent methylation QTLs. Hum. Genet. 2015;134:291-303.

    Not in our library10.1007/s00439-014-1521-6

14. 14.

    Liu R, Jin J-P. Calponin isoforms CNN1, CNN2 and CNN3: regulators for actin cytoskeleton functions in smooth muscle and non-muscle cells. Gene. 2016;585:143-153.

    Not in our library10.1016/j.gene.2016.02.040

15. 15.

    Besnard S, et al. Smooth muscle dysfunction in resistance arteries of the staggerer mouse, a mutant of the nuclear receptor RORα. Circ. Res. 2002;90:820-825.

    Not in our library10.1161/01.res.0000014489.24705.71

16. 16.

    Mikhailov AT, Torrado M. The enigmatic role of the ankyrin repeat domain 1 gene in heart development and disease. Int. J. Dev. Biol. 2008;52:811-821.

    Not in our library10.1387/ijdb.082655am

17. 17.

    Kwapiszewska G, et al. Fhl-1, a new key protein in pulmonary hypertension. Circulation. 2008;118:1183-1194.

    Not in our library10.1161/circulationaha.107.761916

18. 18.

    Geng T, et al. H19 lncRNA promotes skeletal muscle insulin sensitivity in part by targeting AMPK. Diabetes. 2018;67:2183-2198.

    Not in our library10.2337/db18-0370

19. 19.

    Huang L, et al. Critical roles of Xirp proteins in cardiac conduction and their rare variants identified in sudden unexplained nocturnal death syndrome and Brugada syndrome in Chinese Han population. J. Am. Heart Assoc. 2018;7:e006320.

    Not in our library10.1161/jaha.117.006320

20. 20.

    Fittipaldi S, et al. Alpha B-crystallin induction in skeletal muscle cells under redox imbalance is mediated by a JNK-dependent regulatory mechanism. Free Radic. Biol. Med. 2015;86:331-342.

    Not in our library10.1016/j.freeradbiomed.2015.05.035

21. 21.

    Rajakumari S, et al. EBF2 determines and maintains brown adipocyte identity. Cell Metab. 2013;17:562-574.

    Not in our library10.1016/j.cmet.2013.01.015

22. 22.

    2016 AHA late-breaking basic science abstracts. Circ. Res. 119, e160–e171 (2016).

    Not in our library10.1161/res.0000000000000126

23. 23.

    Bolotta A, et al. New insights into the hepcidin-ferroportin axis and iron homeostasis in iPSC-derived cardiomyocytes from Friedreich’s ataxia patient. Oxid. Med. Cell. Longev. 2019;2019:7623023.

    Not in our library10.1155/2019/7623023

24. 24.
    An essential cell-autonomous role for hepcidin in cardiac iron homeostasis · 2016

    No notice
25. 25.

    Medioni C, et al. Expression of Slit and Robo genes in the developing mouse heart. Dev. Dyn. 2010;239:3303-3311.

    Not in our library10.1002/dvdy.22449

26. 26.

    Lee JH, Protze SI, Laksman Z, Backx PH, Keller GM. Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Cell Stem Cell. 2017;21:179-194.e4.

    Not in our library10.1016/j.stem.2017.07.003

27. 27.

    Liu C, Luo N, Tung C-Y, Perrin BJ, Zhao B. GRXCR2 regulates taperin localization critical for stereocilia morphology and hearing. Cell Rep. 2018;25:1268-1280.e4.

    Not in our library10.1016/j.celrep.2018.09.063

28. 28.

    Liu X, et al. Single-cell RNA-Seq of the developing cardiac outflow tract reveals convergent development of the vascular smooth muscle cells. Cell Rep. 2019;28:1346-1361.e4.

    Not in our library10.1016/j.celrep.2019.06.092

29. 29.

    Kalucka J, et al. Single-cell transcriptome atlas of murine endothelial cells. Cell. 2020;180:764-779.e20.

    Not in our library10.1016/j.cell.2020.01.015

30. 30.
    Antigen Presentation by Vascular Cells · 2017

    No notice
31. 31.

    Corada M, Morini MF, Dejana E. Signaling pathways in the specification of arteries and veins. Arterioscler. Thromb. Vasc. Biol. 2014;34:2372-2377.

    Not in our library10.1161/atvbaha.114.303218

32. 32.

    Kashiwazaki M, et al. A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions. Int. Immunol. 2003;15:1219-1227.

    Not in our library10.1093/intimm/dxg121

33. 33.

    Awwad K, et al. Role of secreted modular calcium-binding protein 1 (SMOC1) in transforming growth factor β signalling and angiogenesis. Cardiovasc. Res. 2015;106:284-294.

    Not in our library10.1093/cvr/cvv098

34. 34.

    Tang J, et al. Genetic fate mapping defines the vascular potential of endocardial cells in the adult heart. Circ. Res. 2018;122:984-993.

    Not in our library10.1161/circresaha.117.312354

35. 35.

    Stallcup WB. The NG2 proteoglycan in pericyte biology. Adv. Exp. Med. Biol. 2018;1109:5-19.

    Not in our library10.1007/978-3-030-02601-1_2

36. 36.
    Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells · 2016

    No notice
37. 37.

    Barker N, Clevers H. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology. 2010;138:1681-1696.

    Not in our library10.1053/j.gastro.2010.03.002

38. 38.

    Daniel J-M, et al. Regulator of G-protein signaling 5 prevents smooth muscle cell proliferation and attenuates neointima formation. Arterioscler. Thromb. Vasc. Biol. 2016;36:317-327.

    Not in our library10.1161/atvbaha.115.305974

39. 39.

    Vanlandewijck M, et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature. 2018;554:475-480.

    Not in our library10.1038/nature25739

40. 40.
    It Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease · 2018

    No notice

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