期刊
STEM CELL REPORTS
卷 9, 期 6, 页码 1780-1795出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2017.10.022
关键词
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资金
- Astellas Clinical/Basic Research grant
- Hospital for Sick Children Transplant and Regenerative Medicine Program
- Canadian Institute of Health Research [MOP-57885]
- Ontario Research Fund Global Leadership Round in Genomics and Life Sciences grants
- CIHR Foundation [FDN-143231]
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 progenitorlike 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.
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