biostudies-literatureO hAinmhire ENIDDK NIH HHSChan Zuckerberg InitiativeNIDDKF63-F75https://www.ebi.ac.uk/biostudies/studies/S-EPMC6383201biostudies-literatureUnknown316(1)Glioma-associated oncogene homolog-1 (Gli1)-positive resident mesenchymal stem cell-like cells are the predominant source of kidney myofibroblasts in fibrosis, but investigating Gli1-positive myofibroblast progenitor activation is hampered by the difficulty of isolating and propagating primary cultures of these cells. Using a genetic strategy with positive and negative selection, we isolated Kidney-Gli1 (KGli1) cells that maintain expression of appropriate mesenchymal stem cell-like cell markers, respond to hedgehog pathway activation, and display robust myofibroblast differentiation upon treatment with transforming growth factor-β (TGF-β). Coculture of KGli1 cells with endothelium stabilizes capillary formation. Single-cell RNA sequencing (scRNA-seq) analysis during differentiation identiAmerican journal of physiology. Renal physiologyA conditionally immortalized Gli1-positive kidney mesenchymal cell line models myofibroblast transition.PMC6383201DK076169R01 DK103740DK107374UH3 DK107374U24 DK115255DK115255173970T32 DK007126DK103740Muto YDonnelly ELHumphreys BDMachado FGFan LXO hAinmhire EChang-Panesso MWu HfalseA conditionally immortalized Gli1-positive kidney mesenchymal cell line models myofibroblast transition.Glioma-associated oncogene homolog-1 (Gli1)-positive resident mesenchymal stem cell-like cells are the predominant source of kidney myofibroblasts in fibrosis, but investigating Gli1-positive myofibroblast progenitor activation is hampered by the difficulty of isolating and propagating primary cultures of these cells. Using a genetic strategy with positive and negative selection, we isolated Kidney-Gli1 (KGli1) cells that maintain expression of appropriate mesenchymal stem cell-like cell markers, respond to hedgehog pathway activation, and display robust myofibroblast differentiation upon treatment with transforming growth factor-β (TGF-β). Coculture of KGli1 cells with endothelium stabilizes capillary formation. Single-cell RNA sequencing (scRNA-seq) analysis during differentiation identi2019-01-01T00:00:00Z2019 Jan2026-07-10T03:23:05.218Z2025-05-29T22:28:28.519ZS-EPMC63832013030371210.1152/ajprenal.00460.2018