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Developmental lineage of human pluripotent stem cell‐derived cardiac fibroblasts affects their functional phenotype
Author(s) -
Floy Martha E.,
Givens Sophie E.,
Matthys Oriane B.,
Mateyka Taylor D.,
Kerr Charles M.,
Steinberg Alexandra B.,
Silva Ana C.,
Zhang Jianhua,
Mei Ying,
Ogle Brenda M.,
McDevitt Todd C.,
Kamp Timothy J.,
Palecek Sean P.
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100523r
Subject(s) - induced pluripotent stem cell , microbiology and biotechnology , extracellular matrix , myofibroblast , biology , stem cell , paracrine signalling , phenotype , immunology , embryonic stem cell , fibrosis , pathology , genetics , medicine , gene , receptor
Cardiac fibroblasts (CFBs) support heart function by secreting extracellular matrix (ECM) and paracrine factors, respond to stress associated with injury and disease, and therefore are an increasingly important therapeutic target. We describe how developmental lineage of human pluripotent stem cell‐derived CFBs, epicardial (EpiC‐FB), and second heart field (SHF‐FB) impacts transcriptional and functional properties. Both EpiC‐FBs and SHF‐FBs exhibited CFB transcriptional programs and improved calcium handling in human pluripotent stem cell‐derived cardiac tissues. We identified differences including in composition of ECM synthesized, secretion of growth and differentiation factors, and myofibroblast activation potential, with EpiC‐FBs exhibiting higher stress‐induced activation potential akin to myofibroblasts and SHF‐FBs demonstrating higher calcification and mineralization potential. These phenotypic differences suggest that EpiC‐FBs have utility in modeling fibrotic diseases while SHF‐FBs are a promising source of cells for regenerative therapies. This work directly contrasts regional and developmental specificity of CFBs and informs CFB in vitro model selection.