High-throughput Functional Genomics Identifies Regulators of Primary Human Beta Cell Proliferation

作者:Robitaille Karine; Rourke Jillian L; McBane Joanne E; Fu Accalia; Baird Stephen; Du Qiujiang; Kin Tatsuya; Shapiro A M James; Screaton Robert A
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291(9): 4614-4625.
DOI:10.1074/jbc.M115.683912

摘要

The expansion of cells for regenerative therapy will require the genetic dissection of complex regulatory mechanisms governing the proliferation of non-transformed human cells. Here, we report the development of a high-throughput RNAi screening strategy specifically for use in primary cells and demonstrate that silencing the cell cycle-dependent kinase inhibitors CDKN2C/p18 or CDKN1A/p21 facilitates cell cycle entry of quiescent adult human pancreatic beta cells. This work identifies p18 and p21 as novel targets for promoting proliferation of human beta cells and demonstrates the promise of functional genetic screens for dissecting therapeutically relevant state changes in primary human cells.

  • 出版日期2016-2-26