Characterization of a Common Progenitor Pool of the Epicardium and Myocardium

Overview

Journal Science

Specialty Science

Date 2021 Jan 8

PMID 33414188

Citations 61

Authors

Richard C V Tyser

Ximena Ibarra-Soria

Katie McDole

Satish Arcot Jayaram

Jonathan Godwin

Teun A H van den Brand

Antonio M A Miranda

Antonio Scialdone

Philipp J Keller

John C Marioni

Shankar Srinivas

Affiliations

Soon will be listed here.

Abstract

The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac cell types arise is limited. We mapped the origin of the embryonic mouse heart at single-cell resolution using a combination of transcriptomic, imaging, and genetic lineage labeling approaches. This mapping provided a transcriptional and anatomic definition of cardiac progenitor types. Furthermore, it revealed a cardiac progenitor pool that is anatomically and transcriptionally distinct from currently known cardiac progenitors. Besides contributing to cardiomyocytes, these cells also represent the earliest progenitor of the epicardium, a source of trophic factors and cells during cardiac development and injury. This study provides detailed insights into the formation of early cardiac cell types, with particular relevance to the development of cell-based cardiac regenerative therapies.

Citing Articles

Global, regional, and national burden of congenital heart disease, 1990-2021: a systematic analysis for the global burden of disease study 2021.

Zhang X, Feng Y, Ren J, Jin X, Li J, Hou Y Eur J Pediatr. 2025; 184(4):253.

PMID: 40088268 DOI: 10.1007/s00431-025-06085-w.

Ubiquitous MEIS transcription factors actuate lineage-specific transcription to establish cell fate.

Darieva Z, Zarrineh P, Phillips N, Mallen J, Garcia Mora A, Donaldson I EMBO J. 2025; .

PMID: 40021842 DOI: 10.1038/s44318-025-00385-5.

The Wilms' Tumor Suppressor WT1 in Cardiomyocytes: Implications for Cardiac Homeostasis and Repair.

Diaz Del Moral S, Wagner N, Wagner K Cells. 2025; 13(24.

PMID: 39768169 PMC: 11674098. DOI: 10.3390/cells13242078.

In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between.

Stougiannou T, Christodoulou K, Karangelis D Biomedicines. 2025; 12(12.

PMID: 39767621 PMC: 11726960. DOI: 10.3390/biomedicines12122714.

Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development.

Yuri S, Arisawa N, Kitamuro K, Isotani A iScience. 2024; 27(12):111414.

PMID: 39687030 PMC: 11647242. DOI: 10.1016/j.isci.2024.111414.

References

Lawson K . Fate mapping the mouse embryo. Int J Dev Biol. 2000; 43(7):773-5. View

Nowotschin S, Setty M, Kuo Y, Liu V, Garg V, Sharma R . The emergent landscape of the mouse gut endoderm at single-cell resolution. Nature. 2019; 569(7756):361-367. PMC: 6724221. DOI: 10.1038/s41586-019-1127-1. View

Pijuan-Sala B, Griffiths J, Guibentif C, Hiscock T, Jawaid W, Calero-Nieto F . A single-cell molecular map of mouse gastrulation and early organogenesis. Nature. 2019; 566(7745):490-495. PMC: 6522369. DOI: 10.1038/s41586-019-0933-9. View

Tyser R, Srinivas S . The First Heartbeat-Origin of Cardiac Contractile Activity. Cold Spring Harb Perspect Biol. 2019; 12(7). PMC: 7328461. DOI: 10.1101/cshperspect.a037135. View

Dunwoodie S, Rodriguez T, Beddington R . Msg1 and Mrg1, founding members of a gene family, show distinct patterns of gene expression during mouse embryogenesis. Mech Dev. 1998; 72(1-2):27-40. DOI: 10.1016/s0925-4773(98)00011-2. View

Candia A, Hu J, Crosby J, Lalley P, Noden D, Nadeau J . Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development. 1992; 116(4):1123-36. DOI: 10.1242/dev.116.4.1123. View

Lescroart F, Wang X, Lin X, Swedlund B, Gargouri S, Sanchez-Danes A . Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq. Science. 2018; 359(6380):1177-1181. PMC: 6556615. DOI: 10.1126/science.aao4174. View

McDole K, Guignard L, Amat F, Berger A, Malandain G, Royer L . In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level. Cell. 2018; 175(3):859-876.e33. DOI: 10.1016/j.cell.2018.09.031. View

Lescroart F, Chabab S, Lin X, Rulands S, Paulissen C, Rodolosse A . Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development. Nat Cell Biol. 2014; 16(9):829-40. PMC: 6984965. DOI: 10.1038/ncb3024. View

10.

de Soysa T, Ranade S, Okawa S, Ravichandran S, Huang Y, Salunga H . Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects. Nature. 2019; 572(7767):120-124. PMC: 6719697. DOI: 10.1038/s41586-019-1414-x. View

11.

Burgess R, Rawls A, Brown D, Bradley A, Olson E . Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature. 1996; 384(6609):570-3. DOI: 10.1038/384570a0. View

12.

Tyser R, Miranda A, Chen C, Davidson S, Srinivas S, Riley P . Calcium handling precedes cardiac differentiation to initiate the first heartbeat. Elife. 2016; 5. PMC: 5059139. DOI: 10.7554/eLife.17113. View

13.

Meilhac S, Buckingham M . The deployment of cell lineages that form the mammalian heart. Nat Rev Cardiol. 2018; 15(11):705-724. DOI: 10.1038/s41569-018-0086-9. View

14.

Wang H, Holland P, Takahashi T . Gene profiling of head mesoderm in early zebrafish development: insights into the evolution of cranial mesoderm. Evodevo. 2019; 10:14. PMC: 6612195. DOI: 10.1186/s13227-019-0128-3. View

15.

Li G, Xu A, Sim S, Priest J, Tian X, Khan T . Transcriptomic Profiling Maps Anatomically Patterned Subpopulations among Single Embryonic Cardiac Cells. Dev Cell. 2016; 39(4):491-507. PMC: 5130110. DOI: 10.1016/j.devcel.2016.10.014. View

16.

Reiter J, Alexander J, Rodaway A, Yelon D, Patient R, Holder N . Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev. 1999; 13(22):2983-95. PMC: 317161. DOI: 10.1101/gad.13.22.2983. View

17.

Christoffels V, Mommersteeg M, Trowe M, Prall O, de Gier-de Vries C, Soufan A . Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res. 2006; 98(12):1555-63. DOI: 10.1161/01.RES.0000227571.84189.65. View

18.

Bressan M, Liu G, Mikawa T . Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Science. 2013; 340(6133):744-8. PMC: 3651765. DOI: 10.1126/science.1232877. View

19.

Cao J, Poss K . The epicardium as a hub for heart regeneration. Nat Rev Cardiol. 2018; 15(10):631-647. PMC: 6143401. DOI: 10.1038/s41569-018-0046-4. View

20.

Moses K, DeMayo F, Braun R, Reecy J, Schwartz R . Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice. Genesis. 2002; 31(4):176-80. DOI: 10.1002/gene.10022. View