TY - JOUR
T1 - Identification of a multipotent Twist2-expressing cell population in the adult heart
AU - Min, Yi Li
AU - Jaichander, Priscilla
AU - Sanchez-Ortiz, Efrain
AU - Bezprozvannaya, Svetlana
AU - Malladi, Venkat S.
AU - Cui, Miao
AU - Wang, Zhaoning
AU - Bassel-Duby, Rhonda
AU - Olson, Eric N.
AU - Liu, Ning
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Angela Mobley of the University of Texas Southwestern (UTSW) Flow Cytometry Core Facility, Hanspeter Niederstrasser of the UTSW High Throughput Screening Core, Beibei Chen of the Department of Clinical Sciences and the Bioinformatics Core Facility, (UTSW), John M. Shelton of the UTSW Histopathology Core, and the UTSW Genomics and Microarray Core Facility for technical help and service; Cheryl Nolen for technical assistance; Wei Tan for assistance with rodent surgery; and Drs. Hesham Sadek and Nikhil Munshi for constructive suggestions and advice. This work was supported by NIH Grants AR-067294, HL-130253, HL-138426, and AR-071980; Fondation Leducq Networks of Excellence; and Robert A. Welch
Funding Information:
Foundation Grant 1-0025 (to E.N.O.). N.L. was supported by Beginning-Grant-In-Aid 13BGIA17150004 from the American Heart Association. Y.-L.M. was supported by a Hamon Center for Regenerative Science and Medicine Trainee Fellowship. V.S.M. was supported by Cancer Prevention and Research Institute of Texas Grant RP150596.
Publisher Copyright:
© 2018 National Academy of Sciences. All Rights Reserved.
PY - 2018/9/4
Y1 - 2018/9/4
N2 - Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from Drosophila to mammals. Through lineage tracing of Twist2 (Tw2)-expressing cells with tamoxifen-inducible Tw2-CreERT2 and tdTomato (tdTO) reporter mice, we discovered a unique cell population that progressively contributes to cardiomyocytes (CMs), endothelial cells, and fibroblasts in the adult heart. Clonal analysis confirmed the ability of Tw2-derived tdTO+ (Tw2-tdTO+) cells to form CMs in vitro. Within the adult heart, Tw2-tdTO+ CMs accounted for ∼13% of total CMs, the majority of which resulted from fusion of Tw2-tdTO+ cells with existing CMs. Tw2-tdTO+ cells also contribute to cardiac remodeling after injury. We conclude that Tw2-tdTO+ cells participate in lifelong maintenance of cardiac function, at least in part through de novo formation of CMs and fusion with preexisting CMs, as well as in the genesis of other cellular components of the adult heart.
AB - Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from Drosophila to mammals. Through lineage tracing of Twist2 (Tw2)-expressing cells with tamoxifen-inducible Tw2-CreERT2 and tdTomato (tdTO) reporter mice, we discovered a unique cell population that progressively contributes to cardiomyocytes (CMs), endothelial cells, and fibroblasts in the adult heart. Clonal analysis confirmed the ability of Tw2-derived tdTO+ (Tw2-tdTO+) cells to form CMs in vitro. Within the adult heart, Tw2-tdTO+ CMs accounted for ∼13% of total CMs, the majority of which resulted from fusion of Tw2-tdTO+ cells with existing CMs. Tw2-tdTO+ cells also contribute to cardiac remodeling after injury. We conclude that Tw2-tdTO+ cells participate in lifelong maintenance of cardiac function, at least in part through de novo formation of CMs and fusion with preexisting CMs, as well as in the genesis of other cellular components of the adult heart.
KW - Cardiac progenitors
KW - Cardiomyocytes
KW - Cell fusion
KW - Differentiation
KW - Twist2
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U2 - 10.1073/pnas.1800526115
DO - 10.1073/pnas.1800526115
M3 - Article
C2 - 30127033
AN - SCOPUS:85052753546
VL - 115
SP - E8430-E8439
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 36
ER -