Distinct populations of vascular smooth muscle and sinoatrial progenitors are localized adjacent to pro-epicardium
The developmental potential of cells adjacent to pro-epicardial (PE) cells (pro-EpiCs) that also express pro-EpiC markers is unknown. We apply single-cell mRNA deep sequencing paired with RNAScope validation, bioinformatic analysis, and lineage tracing to determine the heterogeneity and specification of cells in the PE region. We find that the PE region contains three adjacent cell clusters that have distinct gene expression profiles and distinct spatial locations. Cluster 1 is pro-EpiCs, cluster 2 is vascular smooth muscle cell (VSMC)-like cells, and cluster 3 is pacemaker progenitor cells (PMPCs). Generating a PE-region-specific Myrf<sup>DreERT2/+</sup>-knockin line and using Cre-Lox and/or Dre-Rox reporters, we determine that VSMC-like cells localized posterior to the PE region give rise to VSMCs, and PMPCs localized to the PE region proximal to the atrial wall give rise to sinoatrial node cells. Thus, cells in the PE region adjacent to pro-EpiCs are specified to give rise to coronary VSMCs or pacemaker cells.
Authors
- Xianyan Kuang (ORCID: https://orcid.org/0000-0002-5978-647X)
- Xiaochun Long (ORCID: https://orcid.org/0000-0001-9714-0023)
- Changhong Yin (ORCID: https://orcid.org/0000-0002-4360-5320)
- Lianjie Miao (ORCID: https://orcid.org/0000-0002-8286-9783)
- Nikhil C. Munshi (ORCID: https://orcid.org/0000-0002-7344-9795)
- Harold A. Singer (ORCID: https://orcid.org/0000-0001-8554-3239)
- Preethi H. Gunaratne (ORCID: https://orcid.org/0000-0002-6487-3463)
- Anika Nusrat (ORCID: https://orcid.org/0000-0001-6570-5106)
- Bradley K. McConnell (ORCID: https://orcid.org/0000-0001-8712-0336)
- Sylvia Μ. Evans (ORCID: https://orcid.org/0000-0001-5035-3697)
- Robert J. Schwartz (ORCID: https://orcid.org/0000-0001-9202-2984)
- Ashok Kumar (ORCID: https://orcid.org/0000-0001-8571-2848)
- Mingfu Wu (ORCID: https://orcid.org/0000-0003-0155-2328)
- Weihua Huang (ORCID: https://orcid.org/0000-0003-1176-3719)
- Renjie Song
- Jian Li (ORCID: https://orcid.org/0000-0001-7953-8230)
- Bin Zhou (ORCID: https://orcid.org/0000-0001-5278-5522)
- Yangyang Lu (ORCID: https://orcid.org/0000-0002-2933-3461)
- Edward Chin Man Lo (ORCID: https://orcid.org/0000-0002-2518-2686)
- Dan Sun (ORCID: https://orcid.org/0000-0002-6249-5999)
- Zhen-Chuan Fan
Institutions
- Zhejiang International Studies University (CN)
- New York State Department of Health (US)
- Wadsworth Center (US)
- East Carolina University (US)
- Augusta University (US)
- Southwestern Medical Center (US)
- Center for Excellence in Molecular Cell Science (CN)
- Children's Hospital of Fudan University (CN)
- Southwestern Medical Center (US)
- University of Houston (US)
- University of Montana (US)
- Albany Medical Center Hospital (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1016/j.celrep.2025.116580
- Citations
- 1
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 0.81