cKit⁺ cardiac progenitors of neural crest origin

The degree to whichcKit-expressing progenitors generate cardiomyocytes in the heart is controversial. Genetic fate-mapping studies suggest minimal contribution; however, whether or not minimal contribution reflects minimal cardiomyogenic capacity is unclear because the embryonic origin and role in c...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-10, Vol.112 (42), p.13051-13056
Main Authors: Hatzistergos, Konstantinos E., Takeuchi, Lauro M., Saur, Dieter, Seidler, Barbara, Dymecki, Susan M., Mai, Jia Jia, White, Ian A., Balkan, Wayne, Kanashiro-Takeuchi, Rosemeire M., Schally, Andrew V., Hare, Joshua M.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Bone Morphogenetic Proteins - antagonists & inhibitors
Cardiomyocytes
Heart
Mice
Mice, Transgenic
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Neural Crest - cytology
Neural Crest - metabolism
Proteins
Proto-Oncogene Proteins c-kit - genetics
Rodents
Stem cells
Stem Cells - cytology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The degree to whichcKit-expressing progenitors generate cardiomyocytes in the heart is controversial. Genetic fate-mapping studies suggest minimal contribution; however, whether or not minimal contribution reflects minimal cardiomyogenic capacity is unclear because the embryonic origin and role in cardiogenesis of these progenitors remain elusive. Using high-resolution genetic fate-mapping approaches withcKitCreERT2/+ andWnt1::Flpemouse lines, we show thatcKitdelineates cardiac neural crest progenitors (CNC kit ). CNC kit possess full cardiomyogenic capacity and contribute to all CNC derivatives, including cardiac conduction system cells. Furthermore, by modeling cardiogenesis incKitCreERT2 -induced pluripotent stem cells, we show that, paradoxically, the cardiogenic fate of CNC kit is regulated by bone morphogenetic protein antagonism, a signaling pathway activated transiently during establishment of the cardiac crescent, and extinguished from the heart before CNC invasion. Together, these findings elucidate the origin of cKit⁺ cardiac progenitors and suggest that a nonpermissive cardiac milieu, rather than minimal cardiomyogenic capacity, controls the degree of CNC kit contribution to myocardium.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1517201112