Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E8430-E8439 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 115 |
| Issue number | 36 |
| DOIs | |
| State | Published - Sep 4 2018 |
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Keywords
- Cardiac progenitors
- Cardiomyocytes
- Cell fusion
- Differentiation
- Twist2
ASJC Scopus subject areas
- General
Cite this
Identification of a multipotent Twist2-expressing cell population in the adult heart. / Min, Yi Li; Jaichander, Priscilla; Sanchez-Ortiz, Efrain; Bezprozvannaya, Svetlana; Malladi, Venkat S.; Cui, Miao; Wang, Zhaoning; Bassel-Duby, Rhonda; Olson, Eric N.; Liu, Ning.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 36, 04.09.2018, p. E8430-E8439.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=85052753546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052753546&partnerID=8YFLogxK
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 -