在肠道再生过程中,蹑手蹑脚/RPRD1B对再生干细胞分化的调控。

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tingwei Lan, Mengdi Li, Xiaolin Duan, Huihui Jia, Yajun Cao, Yinyin Wang, Fangli Ren, Jianqiu Sheng, Junfeng Xu, Zhijie Chang
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引用次数: 0

摘要

在肠道再生过程中,通过瞬间诱导聚簇素(CLU)表达而定义的再生干细胞(revSCs)迅速扩增并分化为多个IEC谱系。尽管revSC诱导已被充分研究,但调控其分化的机制仍不清楚。在这项研究中,我们证明了爬/ RPRD1B,蛋白高表达的肿瘤和必不可少的crypt-base柱状细胞(CBC)维护,期间revSC分化所需肠道再生。使用绒毛蛋白- crein介导的爬行细胞敲除(Vil-CREPTKO)小鼠,我们发现爬行细胞的缺失导致辐照损伤后的再生失败。有趣的是,在Vil-CREPTKO小鼠中,revsc显著积累,但肠细胞减少。我们的单细胞转录组分析表明,蹑手蹑脚的缺失损害了revSCs的干细胞潜能,抑制了它们向肠细胞和杯状细胞的分化。谱系追踪实验证实了体内缺乏crept的revsc的再生能力降低。在一起,我们的研究结果认为爬在肠道再生revSC分化的重要调节器。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulation of revival stem cell differentiation by CREPT/RPRD1B during intestinal regeneration.

Revival stem cells (revSCs) defined by transient induction of clusterin (CLU) expression rapidly expand and differentiate into multiple IEC lineages during intestinal regeneration. Although revSC induction is well-studied, the mechanisms governing their differentiation remain unclear. In this study, we demonstrate that CREPT/RPRD1B, a protein highly expressed in tumors and essential for crypt-base columnar cell (CBC) maintenance, was required for revSC differentiation during intestinal regeneration. Using Villin-Cre-mediated CREPT knockout (Vil-CREPTKO) mice, we found that CREPT deletion leads to regeneration failure following irradiation-induced damage. Interestingly, revSCs were remarkably accumulated, but enterocytes were decreased in Vil-CREPTKO mice. Our single-cell transcriptome analyses demonstrated that CREPT deletion impaired the stem potential of revSCs and inhibited their differentiation into enterocytes and goblet cells. Lineage tracing experiments confirmed the reduced regenerative capacity of CREPT-deficient revSCs in vivo. Together, our findings identified CREPT as an important regulator of revSC differentiation during intestinal regeneration.

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来源期刊
Cell and Bioscience
Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
10.70
自引率
0.00%
发文量
187
审稿时长
>12 weeks
期刊介绍: Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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