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

Li Guo, Golnaz Karoubi, Pascal Duchesneau, Maria V. Shutova, Hoon Ki Sung, Peter Tonge, Christine Bear, Ian Rogers, Andras Nagy, Thomas K. Waddell

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15 Citations (Scopus)

Abstract

A suitable source of progenitor cells is required to attenuate disease or affect cure. We present an “interrupted reprogramming” strategy to generate “induced progenitor-like (iPL) cells” 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 “interrupted reprogramming” strategy to produce highly specified functional “induced progenitor-like cells” 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.

Original languageEnglish
Pages (from-to)1780-1795
Number of pages16
JournalStem Cell Reports
Volume9
Issue number6
DOIs
Publication statusPublished - 12 Dec 2017
Externally publishedYes

Keywords

  • generation of induced progenitor-like cells

Cite this

Guo, L., Karoubi, G., Duchesneau, P., Shutova, M. V., Sung, H. K., Tonge, P., Bear, C., Rogers, I., Nagy, A., & Waddell, T. K. (2017). Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming. Stem Cell Reports, 9(6), 1780-1795. https://doi.org/10.1016/j.stemcr.2017.10.022