Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.
Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.
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DOI：
10.1016/j.stem.2017.06.014
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发表时间：
2017-07-06
期刊：
影响因子：
23.9
通讯作者：
Kuo CJ
中科院分区：
文献类型：
--
作者：
Yan KS;Gevaert O;Zheng GXY;Anchang B;Probert CS;Larkin KA;Davies PS;Cheng ZF;Kaddis JS;Han A;Roelf K;Calderon RI;Cynn E;Hu X;Mandleywala K;Wilhelmy J;Grimes SM;Corney DC;Boutet SC;Terry JM;Belgrader P;Ziraldo SB;Mikkelsen TS;Wang F;von Furstenberg RJ;Smith NR;Chandrakesan P;May R;Chrissy MAS;Jain R;Cartwright CA;Niland JC;Hong YK;Carrington J;Breault DT;Epstein J;Houchen CW;Lynch JP;Martin MG;Plevritis SK;Curtis C;Ji HP;Li L;Henning SJ;Wong MH;Kuo CJ
据报道，一些细胞群体在体内平衡和损伤诱导的再生过程中具有肠干细胞（ISC）活性。在这里，我们通过比较RNA测序（RNA-seq）探索了推定的小鼠ISC群体之间的相互关系。多个循环ISC群体的转录组与Lgr 5 + ISC（最明确的ISC库）非常相似，但Bmi 1-GFP+细胞是不同的，并且富含肠内分泌（EE）标记物，包括Prox 1。Prox 1-GFP+细胞在体外表现出持续的克隆生长，Prox 1+细胞的谱系追踪显示在体内稳态和辐射诱导的损伤后长寿命的克隆。单细胞mRNA-seq揭示了Prox 1-GFP+细胞的两个子集，其中一个类似于成熟EE细胞，而另一个显示低水平EE基因表达，但共表达簇细胞标志物Lgr 5和Ascl 2，使人联想到保留标记的分泌祖细胞。我们的数据表明，EE谱系，包括成熟的EE细胞，包括一个水库的自我平衡和损伤诱导的ISCs，扩大我们的理解细胞的可塑性和干性。由包括Lgr 5和Bmi 1的不同标记物代表的多个细胞群能够重建肠上皮。使用比较RNA测序和单细胞转录组学，Yan等人将Bmi 1-GFP+和Prox 1+细胞定义为在稳态和损伤诱导再生期间具有肠干细胞活性的肠内分泌谱系细胞。
Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5+ ISCs, the most well-defined ISC pool, but Bmi1-GFP+ cells were distinct and enriched for enteroendocrine (EE) markers including Prox1. Prox1-GFP+ cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1+ cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of Prox1-GFP+ cells, one of which resembled mature EE cells while the other displayed low level EE gene expression but co-expressed tuft cell markers, Lgr5 and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest that the EE lineage, including mature EE cells, comprise a reservoir of homeostatic and injury-inducible ISCs, extending our understanding of cellular plasticity and stemness. Multiple cell populations, represented by distinct markers including Lgr5 and Bmi1, are capable of reconstituting the intestinal epithelium. Using comparative RNA sequencing and single-cell transcriptomics, Yan et al. define Bmi1-GFP+ and Prox1+ cells as enteroendocrine lineage cells that possess intestinal stem cell activity during homeostasis and injury-induced regeneration.
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影响因子：
29.4
作者：
Kokrashvili Z;Rodriguez D;Yevshayeva V;Zhou H;Margolskee RF;Mosinger B
通讯作者：
Mosinger B
影响因子：
23.9
作者：
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Shivdasani RA
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作者：
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2.5
作者：
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通讯作者：
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影响因子：
14.8
作者：
Anchang, Benedict;Hart, Tom D. P.;Plevritis, Sylvia K.
通讯作者：
Plevritis, Sylvia K.