2026-07-05T14:59:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/77262025-05-30T08:42:38Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Zhang, Jianhua author Tao, Ran author Campbell, Katherine F author Carvalho, Juliana L author Ruiz, Edward C author Kim, Gina C author Schmuck, Eric G author Raval, Amish N author da Rocha, André Monteiro author Herron, Todd J author Jalife, Jose author Thomson, James A author Kamp, Timothy J author 2019 Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration. Nat Commun. 2019; 10(1):2238 10.1038/s41467-019-09831-5 2041-1723 2041-1723 Nature communications 31110246 http://hdl.handle.net/20.500.12105/7726 Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors