Cardiac fibroblast sub-types in vitro reflect pathological cardiac remodeling in vivo
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Cardiac fibroblast sub-types in vitro reflect pathological cardiac remodeling in vivo. / Herum, Kate Møller; Weng, Guangzheng; Kahnert, Konstantin; Waikel, Rebekah; Milburn, Greg; Conger, Autumn; Anaya, Paul; Campbell, Kenneth S.; Lundby, Alicia; Won, Kyoung Jae; Brakebusch, Cord.
In: Matrix Biology Plus, Vol. 15, 100113, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cardiac fibroblast sub-types in vitro reflect pathological cardiac remodeling in vivo
AU - Herum, Kate Møller
AU - Weng, Guangzheng
AU - Kahnert, Konstantin
AU - Waikel, Rebekah
AU - Milburn, Greg
AU - Conger, Autumn
AU - Anaya, Paul
AU - Campbell, Kenneth S.
AU - Lundby, Alicia
AU - Won, Kyoung Jae
AU - Brakebusch, Cord
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - Many heart diseases are associated with fibrosis, but it is unclear whether different types of heart disease correlate with different subtypes of activated fibroblasts and to which extent such diversity is modeled during in vitro activation of primary cardiac fibroblasts. Analyzing the expression of 82 fibrosis related genes in 65 heart failure (HF) patients, we identified a panel of 12 genes clearly distinguishing HF patients better from healthy controls than measurement of the collagen-related hydroxyproline content. A subcluster enriched in ischemic HF was recognized, but not for diabetes, high BMI, or gender. Single-cell transcriptomic analysis of in vitro activated mouse cardiac fibroblasts distinguished 6 subpopulations, including a contractile Acta2high precursor population, which was predicted by time trajectory analysis to develop into Acta2low subpopulations with high production of extracellular matrix molecules. The 12 gene profile identified in HF patients showed highest similarity to the fibroblast subset with the strongest expression of extracellular matrix molecules. Population markers identified were furthermore able to clearly cluster different disease stages in a murine model for myocardial infarct. These data suggest that major features of cardiac fibroblast activation in heart failure patients, in murine heart disease models, and in cell culture of primary murine cardiac fibroblast are shared.
AB - Many heart diseases are associated with fibrosis, but it is unclear whether different types of heart disease correlate with different subtypes of activated fibroblasts and to which extent such diversity is modeled during in vitro activation of primary cardiac fibroblasts. Analyzing the expression of 82 fibrosis related genes in 65 heart failure (HF) patients, we identified a panel of 12 genes clearly distinguishing HF patients better from healthy controls than measurement of the collagen-related hydroxyproline content. A subcluster enriched in ischemic HF was recognized, but not for diabetes, high BMI, or gender. Single-cell transcriptomic analysis of in vitro activated mouse cardiac fibroblasts distinguished 6 subpopulations, including a contractile Acta2high precursor population, which was predicted by time trajectory analysis to develop into Acta2low subpopulations with high production of extracellular matrix molecules. The 12 gene profile identified in HF patients showed highest similarity to the fibroblast subset with the strongest expression of extracellular matrix molecules. Population markers identified were furthermore able to clearly cluster different disease stages in a murine model for myocardial infarct. These data suggest that major features of cardiac fibroblast activation in heart failure patients, in murine heart disease models, and in cell culture of primary murine cardiac fibroblast are shared.
KW - Fibrosis
KW - Heart failure
KW - Myofibroblast
U2 - 10.1016/j.mbplus.2022.100113
DO - 10.1016/j.mbplus.2022.100113
M3 - Journal article
C2 - 35719864
AN - SCOPUS:85131757289
VL - 15
JO - Matrix Biology Plus
JF - Matrix Biology Plus
SN - 2590-0285
M1 - 100113
ER -
ID: 313646400