Gentian Lluri1, Vincent Huang2, Marlin Touma3, Xiaoqian Liu2, Andrew W Harmon2, Atsushi Nakano4. 1. Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, Section of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA. 2. Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA. 3. Children's Discovery and Innovation Institute Department of Pediatrics, Department of Molecular Cell and Integrative Physiology, David Geffen School of Medicine, USA. 4. Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: anakano@ucla.edu.
Abstract
RATIONALE: During embryogenesis, hematopoietic cells appear in the myocardium prior to the initiation of coronary formation. However, their role is unknown. OBJECTIVE: Here we investigate whether pre-existing hematopoietic cells are required for the formation of coronary vasculature. METHODS AND RESULTS: As a model of for hematopoietic cell deficient animals, we used Runx1 knockout embryos and Vav1-cre; R26-DTA embryos, latter of which genetically ablates 2/3 of CD45(+) hematopoietic cells. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Interestingly, in both models it appears that epicardial to mesenchymal transition is adversely affected in the absence of hematopoietic progenitors. CONCLUSION: Hematopoietic cells are not merely passively transported via coronary vessel, but substantially involved in the induction of the coronary growth. Our findings suggest a novel mechanism of coronary growth.
RATIONALE: During embryogenesis, hematopoietic cells appear in the myocardium prior to the initiation of coronary formation. However, their role is unknown. OBJECTIVE: Here we investigate whether pre-existing hematopoietic cells are required for the formation of coronary vasculature. METHODS AND RESULTS: As a model of for hematopoietic cell deficient animals, we used Runx1 knockout embryos and Vav1-cre; R26-DTA embryos, latter of which genetically ablates 2/3 of CD45(+) hematopoietic cells. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Interestingly, in both models it appears that epicardial to mesenchymal transition is adversely affected in the absence of hematopoietic progenitors. CONCLUSION: Hematopoietic cells are not merely passively transported via coronary vessel, but substantially involved in the induction of the coronary growth. Our findings suggest a novel mechanism of coronary growth.
Authors: Tamar C Katz; Manvendra K Singh; Karl Degenhardt; José Rivera-Feliciano; Randy L Johnson; Jonathan A Epstein; Clifford J Tabin Journal: Dev Cell Date: 2012-03-13 Impact factor: 12.270
Authors: Cindy L Grines; Matthew W Watkins; John J Mahmarian; Ami E Iskandrian; Jeffrey J Rade; Pran Marrott; Craig Pratt; Neal Kleiman Journal: J Am Coll Cardiol Date: 2003-10-15 Impact factor: 24.094
Authors: Bingruo Wu; Zheng Zhang; Wendy Lui; Xiangjian Chen; Yidong Wang; Alyssa A Chamberlain; Ricardo A Moreno-Rodriguez; Roger R Markwald; Brian P O'Rourke; David J Sharp; Deyou Zheng; Jack Lenz; H Scott Baldwin; Ching-Pin Chang; Bin Zhou Journal: Cell Date: 2012-11-21 Impact factor: 41.582
Authors: James A Stefater; Ian Lewkowich; Sujata Rao; Giovanni Mariggi; April C Carpenter; Adam R Burr; Jieqing Fan; Rieko Ajima; Jeffery D Molkentin; Bart O Williams; Marsha Wills-Karp; Jeffrey W Pollard; Terry Yamaguchi; Napoleone Ferrara; Holger Gerhardt; Richard A Lang Journal: Nature Date: 2011-05-29 Impact factor: 49.962
Authors: Alexandra Riddell; Martin McBride; Thomas Braun; Stuart A Nicklin; Ewan Cameron; Christopher M Loughrey; Tamara P Martin Journal: Cardiovasc Res Date: 2020-07-01 Impact factor: 10.787