Profiling proliferative cells and their progeny in damaged murine hearts

被引：143

作者：

Kretzschmar, Kai ^{[1
,2
,3
]}

Post, Yorick ^{[1
,2
]}

Bannier-Helaouet, Marie ^{[1
,2
,3
,4
]}

Mattiotti, Andrea ^{[5
]}

Drost, Jarno ^{[1
,2
,6
]}

Basak, Onur ^{[1
,2
,7
,8
]}

Li, Vivian S. W. ^{[1
,2
,9
]}

van den Born, Maaike ^{[1
,2
,3
]}

Gunst, Quinn D. ^{[5
]}

Versteeg, Danielle ^{[1
,2
]}

Kooijman, Lieneke ^{[1
,2
]}

van der Elst, Stefan ^{[1
,2
]}

van Es, Johan H. ^{[1
,2
,3
]}

van Rooij, Eva ^{[1
,2
,10
]}

van den Hoff, Maurice J. B. ^{[5
]}

Clevers, Hans ^{[1
,2
,3
,6
]}

机构：

[1] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[3] Hubrecht Inst, Oncode Inst, NL-3584 CT Utrecht, Netherlands

[4] Ecole Normale Super Lyon, Dept Biol, F-69007 Lyon, France

[5] Amsterdam Univ Med Ctr, Acad Med Ctr, Dept Med Physiol, NL-1105 AZ Amsterdam, Netherlands

[6] Princess Maxima Ctr Pediat Oncol, NL-3584 CT Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands

[8] Univ Utrecht, NL-3584 CG Utrecht, Netherlands

[9] Francis Crick Inst, London NW1 1AT, England

[10] Univ Med Ctr Utrecht, Mol Cardiol, NL-3584 CG Utrecht, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 52期

关键词：

stem cells; lineage tracing; cardiac regeneration; fibroblasts; single-cell transcriptomics; CARDIAC STEM-CELLS; IN MICE FAIL; ADULT; REGENERATION; EXPRESSION; CYCLE; CARDIOMYOCYTES; POPULATION; MULTIPOTENT; SUFFICIENT;

D O I：

10.1073/pnas.1805829115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：E12245 / E12254

页数：10

共 54 条

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