@article{257d40293a7c4dc8bb59e6951f6a504c,
title = "Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4",
abstract = "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.",
keywords = "BMP2 and Cxcl12/Cxc4 signaling, coronary vessels, endocardium, heart regeneration",
author = "Gaetano D'Amato and Ragini Phansalkar and Naftaly, {Jeffrey A.} and Xiaochen Fan and Amir, {Zhainib A.} and {Rios Coronado}, {Pamela E.} and Cowley, {Dale O.} and Quinn, {Kelsey E.} and Bikram Sharma and Caron, {Kathleen M.} and Alessandra Vigilante and Kristy Red-Horse",
note = "Funding Information: Grant support: K.R.-H., NIH/NHLBL ( R01-HL128503 ) and they are an HHMI Investigator; G.D{\textquoteright}A., EMBO ( ALTF 1542-2016 ) and NIH ( T32HL120824 ); R.P., AHA graduate fellowship ; J.A.N. and Z.A.A., NIGMS, NIH T32GM007276 ); P.E.R.C., NIGMS, NIH T32GM007276 ) and NSF -GRFP (DGE-1656518); Stanford Genome Sequencing Services Center , NIH ( S10OD020141 ). We thank Ralf Adams for BmxCreER, Jos{\'e} Luis de la Pompa for ISH reagents, Rahul Sinha for experimental assistance, and all members of the Red-Horse lab for technical and intellectual support. Funding Information: Grant support: K.R.-H. NIH/NHLBL (R01-HL128503) and they are an HHMI Investigator; G.D'A. EMBO (ALTF 1542-2016) and NIH (T32HL120824); R.P. AHA graduate fellowship; J.A.N. and Z.A.A. NIGMS, NIH T32GM007276); P.E.R.C. NIGMS, NIH T32GM007276) and NSF-GRFP (DGE-1656518); Stanford Genome Sequencing Services Center, NIH (S10OD020141). We thank Ralf Adams for BmxCreER, Jos{\'e} Luis de la Pompa for ISH reagents, Rahul Sinha for experimental assistance, and all members of the Red-Horse lab for technical and intellectual support. G.D'A. and K.R.-H. conceptualized the study and wrote the article. G.D'A. R.P. J.A.N. X.F. and Z.A.A. performed experiments. G.D'A. and A.V. performed computational analysis. G.D'A. K.R.-H. K.E.Q. and K.M.C. designed Cxcr4-Tango and provided experimental resources. D.O.C. advised on and generated Cxcr4-Tango. B.S. provided experimental and manuscript assistance. P.E.R.C. assisted with the neonatal injured hearts. All authors reviewed the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = nov,
day = "21",
doi = "10.1016/j.devcel.2022.10.007",
language = "English",
volume = "57",
pages = "2517--2532.e6",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "22",
}