Developmental lineage of human pluripotent stem cell‐derived cardiac fibroblasts affects their functional phenotype

• DOI: 10.1096/fj.202100523r
• Publication Date: 2021-08-02T17:06:10Z
• Authors: Martha E. Floy; Sophie E. Givens; Oriane B. Matthys; Taylor D. Mateyka; Charles M. Kerr; Alexandra B. Stei...; Ana C. Silva; Jianhua Zhang; Ying Mei; Brenda M. Ogle; Todd C. McDevitt; Timothy J. Kamp; Sean P. Palecek
• Keywords: Myofibroblast

Cardiac fibroblasts (CFBs) support heart function by secreting extracellular matrix (ECM) and paracrine factors, respond to stress associated with injury disease, therefore are an increasingly important therapeutic target. We describe how developmental lineage of human pluripotent stem cell-derived CFBs, epicardial (EpiC-FB), second field (SHF-FB) impacts transcriptional functional properties. Both EpiC-FBs SHF-FBs exhibited CFB programs improved calcium handling in cardiac tissues. identified differences including composition ECM synthesized, secretion growth differentiation myofibroblast activation potential, exhibiting higher stress-induced potential akin myofibroblasts demonstrating calcification mineralization potential. These phenotypic suggest that have utility modeling fibrotic diseases while a promising source cells for regenerative therapies. This work directly contrasts regional specificity CFBs informs vitro model selection.