Jeff Naftaly

All Publications

• Vascular organoids get a speed boost for regenerative repair. Cell stem cell Klinger, D., Naftaly, J. A., Red-Horse, K. 2025; 32 (8): 1185-1187

  Abstract

  Gong et al. present a transcription factor-guided 3D differentiation that rapidly generates vascular organoids from human iPSCs, enhancing engraftment and revascularization of ischemic limbs and transplanted pancreatic islets in mouse models.1 This approach establishes a scalable platform for generating functional vasculature, supporting both disease modeling and regenerative therapy development.

  View details for DOI 10.1016/j.stem.2025.07.002

  View details for PubMedID 40780186

• CXCL12 drives natural variation in coronary artery anatomy across diverse populations. Cell Rios Coronado, P. E., Zhou, J., Fan, X., Zanetti, D., Naftaly, J. A., Prabala, P., Martínez Jaimes, A. M., Farah, E. N., Kundu, S., Deshpande, S. S., Evergreen, I., Kho, P. F., Ma, Q., Hilliard, A. T., Abramowitz, S., Pyarajan, S., Dochtermann, D., Damrauer, S. M., Chang, K. M., Levin, M. G., Winn, V. D., Paşca, A. M., Plomondon, M. E., Waldo, S. W., Tsao, P. S., Kundaje, A., Chi, N. C., Clarke, S. L., Red-Horse, K., Assimes, T. L. 2025

  Abstract

  Coronary arteries have a specific branching pattern crucial for oxygenating heart muscle. Among humans, there is natural variation in coronary anatomy with respect to perfusion of the inferior/posterior left heart, which can branch from either the right arterial tree, the left, or both-a phenotype known as coronary dominance. Using angiographic data for >60,000 US veterans of diverse ancestry, we conducted a genome-wide association study of coronary dominance, revealing moderate heritability and identifying ten significant loci. The strongest association occurred near CXCL12 in both European- and African-ancestry cohorts, with downstream analyses implicating effects on CXCL12 expression. We show that CXCL12 is expressed in human fetal hearts at the time dominance is established. Reducing Cxcl12 in mice altered coronary dominance and caused septal arteries to develop away from Cxcl12 expression domains. These findings indicate that CXCL12 patterns human coronary arteries, paving the way for "medical revascularization" through targeting developmental pathways.

  View details for DOI 10.1016/j.cell.2025.02.005

  View details for PubMedID 40049164

• Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4. Developmental cell D'Amato, G., Phansalkar, R., Naftaly, J. A., Fan, X., Amir, Z. A., Rios Coronado, P. E., Cowley, D. O., Quinn, K. E., Sharma, B., Caron, K. M., Vigilante, A., Red-Horse, K. 2022

  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.

  View details for DOI 10.1016/j.devcel.2022.10.007

  View details for PubMedID 36347256