Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming

Autor: Li Guo, Golnaz Karoubi, Pascal Duchesneau, Maria V. Shutova, Hoon-Ki Sung, Peter Tonge, Christine Bear, Ian Rogers, Andras Nagy, Thomas K. Waddell
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Stem Cell Reports, Vol 9, Iss 6, Pp 1780-1795 (2017)
Druh dokumentu: article
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2017.10.022
Popis: Summary: A suitable source of progenitor cells is required to attenuate disease or affect cure. We present an âinterrupted reprogrammingâ strategy to generate âinduced progenitor-like (iPL) cellsâ using carefully timed expression of induced pluripotent stem cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc; OSKM) from non-proliferative Club cells. Interrupted reprogramming allowed controlled expansion yet preservation of lineage commitment. Under clonogenic conditions, iPL cells expanded and functioned as a bronchiolar progenitor-like population to generate mature Club cells, mucin-producing goblet cells, and cystic fibrosis transmembrane conductance regulator (CFTR)-expressing ciliated epithelium. In vivo, iPL cells can repopulate CFTR-deficient epithelium. This interrupted reprogramming process could be metronomically applied to achieve controlled progenitor-like proliferation. By carefully controlling the duration of expression of OSKM, iPL cells do not become pluripotent, and they maintain their memory of origin and retain their ability to efficiently return to their original phenotype. A generic technique to produce highly specified populations may have significant implications for regenerative medicine. : In this article Waddell, Nagy, and colleagues present an âinterrupted reprogrammingâ strategy to produce highly specified functional âinduced progenitor-like cellsâ from mature quiescent cells. They propose that careful control of the duration of transient expression of iPSC reprogramming factors (OSKM) allows controlled expansion yet preservation of parental lineage without traversing the pluripotent state. Keywords: generation of induced progenitor-like cells
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