Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4

Gaetano D'Amato, Ragini Phansalkar, Jeffrey A. Naftaly, Xiaochen Fan, Zhainib A. Amir, Pamela E. Rios Coronado, Dale O. Cowley, Kelsey E. Quinn, Bikram Sharma, Kathleen M. Caron, Alessandra Vigilante, Kristy Red-Horse*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Endocardial cells lining the heart lumen are coronary vessel progenitors during embryogenesis. Re-igniting this developmental process in adults could regenerate blood vessels lost during cardiac injury, but this requires additional knowledge of molecular mechanisms. Here, we use mouse genetics and scRNA-seq to identify regulators of endocardial angiogenesis and precisely assess the role of CXCL12/CXCR4 signaling. Time-specific lineage tracing demonstrated that endocardial cells differentiated into coronary endothelial cells primarily at mid-gestation. A new mouse line reporting CXCR4 activity—along with cell-specific gene deletions—demonstrated it was specifically required for artery morphogenesis rather than angiogenesis. Integrating scRNA-seq data of endocardial-derived coronary vessels from mid- and late-gestation identified a Bmp2-expressing transitioning population specific to mid-gestation. Bmp2 stimulated endocardial angiogenesis in vitro and in injured neonatal mouse hearts. Our data demonstrate how understanding the molecular mechanisms underlying endocardial angiogenesis can identify new potential therapeutic targets promoting revascularization of the injured heart.

Original languageEnglish
Pages (from-to)2517-2532.e6
JournalDevelopmental Cell
Issue number22
Publication statusPublished - 21 Nov 2022


  • BMP2 and Cxcl12/Cxc4 signaling
  • coronary vessels
  • endocardium
  • heart regeneration


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