美国丹娜-法伯癌症研究院Ramesh A. Shivdasani研究团队在研究中取得进展。他们揭示了Ascl2依赖的细胞去分化驱动肠干细胞的再生。这一研究成果于2020年2月20日在线发表在《细胞—干细胞》杂志上。

Title: Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells

Author: Kazutaka Murata, Unmesh Jadhav, Shariq Madha, Johan van Es, Justin Dean, Alessia Cavazza, Kai Wucherpfennig, Franziska Michor, Hans Clevers, Ramesh A. Shivdasani

Issue&Volume: 2020-02-20

Abstract: Ablation of LGR5+ intestinal stem cells (ISCs) is associated with rapid restoration of the ISC compartment.Different intestinal crypt populations dedifferentiate to provide new ISCs, but thetranscriptional and signaling trajectories that guide this process are unclear, anda large body of work suggests that quiescent “reserve” ISCs contribute to regeneration.By timing the interval between LGR5+ lineage tracing and lethal injury, we show that ISC regeneration is explained nearlycompletely by dedifferentiation, with contributions from absorptive and secretoryprogenitors. The ISC-restricted transcription factor ASCL2 confers measurable competitiveadvantage to resting ISCs and is essential to restore the ISC compartment. Regeneratingcells re-express Ascl2 days before Lgr5, and single-cell RNA sequencing (scRNA-seq) analyses reveal transcriptional pathsunderlying dedifferentiation. ASCL2 target genes include the interleukin-11 (IL-11)receptor Il11ra1, and recombinant IL-11 enhances crypt cell regenerative potential. These findingsreveal cell dedifferentiation as the principal means for ISC restoration and highlightan ASCL2-regulated signal that enables this adaptive response.

DOI: 10.1016/j.stem.2019.12.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30569-7