title: Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors.
abstract: Several studies have reported reprogramming of fibroblasts into induced cardiomyocytes; however, reprogramming into proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of 11 or 5 cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult mouse cardiac, lung, and tail tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors that could be expanded extensively while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells, and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Pratik A
authors.initials: PA
authors.lastname: Lalit
authors.affiliation: Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI 53705, USA; Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53705, USA; Material Science Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Max R
authors.initials: MR
authors.lastname: Salick
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Daryl O
authors.initials: DO
authors.lastname: Nelson
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Jayne M
authors.initials: JM
authors.lastname: Squirrell
authors.affiliation: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Shafer
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Neel G
authors.initials: NG
authors.lastname: Patel
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Imaan
authors.initials: I
authors.lastname: Saeed
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Schmuck
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Yogananda S
authors.initials: YS
authors.lastname: Markandeya
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Lea
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hacker
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI 53705, USA; Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53705, USA; Material Science Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Crone
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
authors.affiliation: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Downs
authors.affiliation: Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Lyons
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: tjk@medicine.wisc.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kamp
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014157:Transcription Factors