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新研究绘制出单细胞分辨率下人类肠道微环境的发育图谱
作者:小柯机器人 发布时间:2020/12/9 13:32:16

美国密歇根大学医学院Jason R. Spence小组研绘制出单细胞分辨率下人类肠道微环境的发育图谱。2020年12月4日,《细胞—干细胞》杂志在线发表了这项成果。

研究人员通过单细胞mRNA测序和原位验证方法来检测了受孕后7–21周的人类肠道发育,为构成微环境的细胞和因子赋予了分子身份和空间位置。WNT和RSPONDIN配体的来源是肌层粘膜的平滑肌细胞,非常接近增殖性隐窝,而绒毛上皮中的EGF却远离隐窝。

取而代之的是,PDGFRAHI/F3HI/DLL1HI间充质群体位于隐窝-绒毛轴上,并且是表皮生长因子(EGF)家族成员NEUREGULIN1(NRG1)的来源。在发育中的肠类器官培养物中,NRG1(而非EGF)通过分泌谱系的分化增加了细胞的多样性。

这项工作强调了肠道EGF/ERBB信号的复杂性,并描绘了关键的微环境细胞和发育中的肠道信号。

据悉,人类肠道干细胞的微环境促进自我更新和上皮功能,但对其发育了解甚少。

附:英文原文

Title: Mapping Development of the Human Intestinal Niche at Single-Cell Resolution

Author: Emily M. Holloway, Michael Czerwinski, Yu-Hwai Tsai, Joshua H. Wu, Angeline Wu, Charlie J. Childs, Katherine D. Walton, Caden W. Sweet, Qianhui Yu, Ian Glass, Barbara Treutlein, J. Gray Camp, Jason R. Spence

Issue&Volume: 2020-12-04

Abstract: The human intestinal stem cell niche supports self-renewal and epithelial function,but little is known about its development. We used single-cell mRNA sequencing within situ validation approaches to interrogate human intestinal development from 7–21 weekspost conception, assigning molecular identities and spatial locations to cells andfactors that comprise the niche. Smooth muscle cells of the muscularis mucosa, in close proximity to proliferative crypts, are a source of WNT and RSPONDIN ligands, whereas EGF is expressed far from crypts in the villus epithelium. Instead, an PDGFRAHI/F3HI/DLL1HI mesenchymal population lines the crypt-villus axis and is the source of the epidermalgrowth factor (EGF) family member NEUREGULIN1 (NRG1). In developing intestine enteroid cultures, NRG1, but not EGF, permitted increasedcellular diversity via differentiation of secretory lineages. This work highlightsthe complexities of intestinal EGF/ERBB signaling and delineates key niche cells andsignals of the developing intestine.

DOI: 10.1016/j.stem.2020.11.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30546-4

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx