Paneth Cell Multipotency Induced by Notch Activation following Injury.
Paneth Cell Multipotency Induced by Notch Activation following Injury.
复制标题
DOI：
10.1016/j.stem.2018.05.002
复制
发表时间：
2018-07-05
期刊：
影响因子：
23.9
通讯作者：
Gao N
中科院分区：
文献类型：
--
作者：
Yu S;Tong K;Zhao Y;Balasubramanian I;Yap GS;Ferraris RP;Bonder EM;Verzi MP;Gao N
潘氏细胞是有丝分裂后肠上皮细胞，支持干细胞生态位和粘膜免疫。在各种胃肠道疾病中观察到潘氏细胞病理，但其可塑性以及对基因组和环境挑战的反应仍不清楚。使用在小鼠 Lyz1 位点设计的敲入等位基因，我们进行了详细的潘氏细胞谱系追踪。辐射诱导一部分潘氏细胞增殖并分化为绒毛上皮细胞。 RNA-seq 揭示从受辐射小鼠分选的潘氏细胞获得了类似干细胞的转录组；当在体外培养时，这些单独的潘氏细胞形成类器官。辐射激活了Notch信号传导，并强制潘氏细胞中Notch胞内结构域（NICD）的表达，但没有激活Wnt/β-连环蛋白途径，从而诱导了它们的去分化。这项研究记录了潘氏细胞的可塑性，特别是它们在干细胞丢失后参与上皮细胞补充的能力，增加了越来越多的知识体系，详细说明了控制损伤诱导再生的分子途径。简而言之：Yu 等人使用在小鼠 Lyz1 位点设计的敲入等位基因。报道称，辐射诱导一部分潘氏细胞去分化。该过程也可以通过在该细胞类型中表达活性 Notch1 来诱导。该研究记录了潘氏细胞的可塑性，扩展了目前对肠道再生的理解。
Paneth cells are post-mitotic intestinal epithelial cells supporting the stem cell niche and mucosal immunity. Paneth cell pathologies are observed in various gastrointestinal diseases, however their plasticity and response to genomic and environmental challenges remains unclear. Using a knock-in allele engineered at the mouse Lyz1 locus, we performed detailed Paneth cell-lineage tracing. Irradiation induced a subset of Paneth cells to proliferate and differentiate into villus epithelial cells. RNA-seq revealed that Paneth cells sorted from irradiated mice acquired a stem cell-like transcriptome; when cultured in vitro, these individual Paneth cells formed organoids. Irradiation activated Notch signaling, and forced expression of Notch intracellular domain (NICD) in Paneth cells, but not Wnt/beta-catenin pathway activation, induced their dedifferentiation. This study documents Paneth cell plasticity, particularly their ability to participate in epithelial replenishment following stem cell loss, adding to a growing body of knowledge detailing the molecular pathways controlling injury-induced regeneration. In Brief: Using a knock-in allele engineered at the mouse Lyz1 locus, Yu et al. report that irradiation induces a subset of Paneth cells to dedifferentiate. This process can also be induced by expressing active Notch1 in this cell type. The study documents Paneth cell plasticity, expanding current understanding of intestinal regeneration.
登录
查看更多内容
影响因子：
64.8
作者：
Karin M;Clevers H
通讯作者：
Clevers H
影响因子：
23.9
作者：
Jadhav U;Saxena M;O'Neill NK;Saadatpour A;Yuan GC;Herbert Z;Murata K;Shivdasani RA
通讯作者：
Shivdasani RA
影响因子：
64.8
作者：
Buczacki, Simon J. A.;Zecchini, Heather Ireland;Winton, Douglas J.
通讯作者：
Winton, Douglas J.
影响因子：
64.8
作者：
Gregorieff, Alex;Liu, Yu;Wrana, Jeffrey L.
通讯作者：
Wrana, Jeffrey L.
影响因子：
64.8
作者：
通讯作者：
--