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Cell Rep. 2017 Dec 5;21(10):2649-2660. doi: 10.1016/j.celrep.2017.11.029.

Cell Type of Origin Dictates the Route to Pluripotency.

Author information

1
Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Wellington Road, Clayton, VIC 3800, Australia; Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
2
ARC Center of Excellence in Plant Energy Biology, University of Western Australia, Perth, WA 6009, Australia; Harry Perkins Institute of Medical Research, Perth, WA 6009, Australia.
3
Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, VIC 3800, Australia; Biomedical Manufacturing, CSIRO Manufacturing, Clayton, VIC 3169, Australia.
4
Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, 8 College Road, 169857 Singapore, Singapore.
5
Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Wellington Road, Clayton, VIC 3800, Australia.
6
Monash Bioinformatics Platform, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
7
Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, 8 College Road, 169857 Singapore, Singapore. Electronic address: owen.rackham@duke-nus.edu.sg.
8
Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Wellington Road, Clayton, VIC 3800, Australia; Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, VIC 3800, Australia. Electronic address: jose.polo@monash.edu.

Abstract

Our current understanding of induced pluripotent stem cell (iPSC) generation has almost entirely been shaped by studies performed on reprogramming fibroblasts. However, whether the resulting model universally applies to the reprogramming process of other cell types is still largely unknown. By characterizing and profiling the reprogramming pathways of fibroblasts, neutrophils, and keratinocytes, we unveil that key events of the process, including loss of original cell identity, mesenchymal to epithelial transition, the extent of developmental reversion, and reactivation of the pluripotency network, are to a large degree cell-type specific. Thus, we reveal limitations for the use of fibroblasts as a universal model for the study of the reprogramming process and provide crucial insights about iPSC generation from alternative cell sources.

KEYWORDS:

Egr1; fibroblasts; induced pluripotent stem cells; keratinocytes; neutrophils; reprogramming; transcriptional dynamics

PMID:
29212013
DOI:
10.1016/j.celrep.2017.11.029
[Indexed for MEDLINE]
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