TY - JOUR
T1 - Profiling proliferative cells and their progeny in damaged murine hearts
AU - Kretzschmar, Kai
AU - Post, Yorick
AU - Bannier-Hélaouët, Marie
AU - Mattiotti, Andrea
AU - Drost, Jarno
AU - Basak, Onur
AU - Li, Vivian S. W.
AU - van den Born, Maaike
AU - Gunst, Quinn D.
AU - Versteeg, Danielle
AU - Kooijman, Lieneke
AU - van der Elst, Stefan
AU - van Es, Johan H.
AU - van Rooij, Eva
AU - van den Hoff, Maurice J. B.
AU - Clevers, Hans
PY - 2018
Y1 - 2018
N2 - The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.
AB - The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85059214060&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30530645
U2 - https://doi.org/10.1073/pnas.1805829115
DO - https://doi.org/10.1073/pnas.1805829115
M3 - Article
C2 - 30530645
SN - 0027-8424
VL - 115
SP - E12245-E12254
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
IS - 52
ER -