Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

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 si...

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Published in:	Cell stem cell Vol. 18; no. 3; p. 354
Main Authors:	Lalit, Pratik A, Salick, Max R, Nelson, Daryl O, Squirrell, Jayne M, Shafer, Christina M, Patel, Neel G, Saeed, Imaan, Schmuck, Eric G, Markandeya, Yogananda S, Wong, Rachel, Lea, Martin R, Eliceiri, Kevin W, Hacker, Timothy A, Crone, Wendy C, Kyba, Michael, Garry, Daniel J, Stewart, Ron, Thomson, James A, Downs, Karen M, Lyons, Gary E, Kamp, Timothy J
Format:	Journal Article
Language:	English
Published:	United States 03.03.2016
Subjects:	Animals Cell Proliferation Cell Survival Cellular Reprogramming Cellular Reprogramming Techniques - methods Fibroblasts - cytology Fibroblasts - metabolism Mice Mice, Transgenic Myoblasts, Cardiac - cytology Myoblasts, Cardiac - metabolism Transcription Factors - biosynthesis Transcription Factors - genetics
ISSN:	1875-9777, 1875-9777
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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.
AbstractList	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.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. 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.
Author	Lyons, Gary E Stewart, Ron Downs, Karen M Eliceiri, Kevin W Crone, Wendy C Garry, Daniel J Patel, Neel G Squirrell, Jayne M Wong, Rachel Lea, Martin R Kamp, Timothy J Lalit, Pratik A Saeed, Imaan Schmuck, Eric G Thomson, James A Kyba, Michael Nelson, Daryl O Shafer, Christina M Hacker, Timothy A Salick, Max R Markandeya, Yogananda S
Author_xml	– sequence: 1 givenname: Pratik A surname: Lalit fullname: Lalit, Pratik A organization: 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 – sequence: 2 givenname: Max R surname: Salick fullname: Salick, Max R organization: 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 – sequence: 3 givenname: Daryl O surname: Nelson fullname: Nelson, Daryl O organization: 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 – sequence: 4 givenname: Jayne M surname: Squirrell fullname: Squirrell, Jayne M organization: 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 – sequence: 5 givenname: Christina M surname: Shafer fullname: Shafer, Christina M organization: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 6 givenname: Neel G surname: Patel fullname: Patel, Neel G organization: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 7 givenname: Imaan surname: Saeed fullname: Saeed, Imaan organization: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 8 givenname: Eric G surname: Schmuck fullname: Schmuck, Eric G organization: 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 – sequence: 9 givenname: Yogananda S surname: Markandeya fullname: Markandeya, Yogananda S organization: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 10 givenname: Rachel surname: Wong fullname: Wong, Rachel organization: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 11 givenname: Martin R surname: Lea fullname: Lea, Martin R organization: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 12 givenname: Kevin W surname: Eliceiri fullname: Eliceiri, Kevin W organization: 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 – sequence: 13 givenname: Timothy A surname: Hacker fullname: Hacker, Timothy A organization: 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 – sequence: 14 givenname: Wendy C surname: Crone fullname: Crone, Wendy C organization: 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 – sequence: 15 givenname: Michael surname: Kyba fullname: Kyba, Michael organization: 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 – sequence: 16 givenname: Daniel J surname: Garry fullname: Garry, Daniel J organization: Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA – sequence: 17 givenname: Ron surname: Stewart fullname: Stewart, Ron organization: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA – sequence: 18 givenname: James A surname: Thomson fullname: Thomson, James A organization: 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 – sequence: 19 givenname: Karen M surname: Downs fullname: Downs, Karen M organization: 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 – sequence: 20 givenname: Gary E surname: Lyons fullname: Lyons, Gary E organization: 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 – sequence: 21 givenname: Timothy J surname: Kamp fullname: Kamp, Timothy J email: tjk@medicine.wisc.edu organization: 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
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SubjectTerms	Animals Cell Proliferation Cell Survival Cellular Reprogramming Cellular Reprogramming Techniques - methods Fibroblasts - cytology Fibroblasts - metabolism Mice Mice, Transgenic Myoblasts, Cardiac - cytology Myoblasts, Cardiac - metabolism Transcription Factors - biosynthesis Transcription Factors - genetics
Title	Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors
URI	https://www.ncbi.nlm.nih.gov/pubmed/26877223 https://www.proquest.com/docview/1770876480
Volume	18
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