新研究繪製出單細胞解析度下人類腸道微環境的發育圖譜
作者：
小柯機器人發布時間：2020/12/9 13:32:16
美國密西根大學醫學院Jason R. Spence小組研繪製出單細胞解析度下人類腸道微環境的發育圖譜。2020年12月4日，《細胞—幹細胞》雜誌在線發表了這項成果。
研究人員通過單細胞mRNA測序和原位驗證方法來檢測了受孕後7–21周的人類腸道發育，為構成微環境的細胞和因子賦予了分子身份和空間位置。WNT和RSPONDIN配體的來源是肌層黏膜的平滑肌細胞，非常接近增殖性隱窩，而絨毛上皮中的EGF卻遠離隱窩。
取而代之的是，PDGFRAHI/F3HI/DLL1HI間充質群體位於隱窩-絨毛軸上，並且是表皮生長因子（EGF）家族成員NEUREGULIN1（NRG1）的來源。在發育中的腸類器官培養物中，NRG1（而非EGF）通過分泌譜系的分化增加了細胞的多樣性。
這項工作強調了腸道EGF/ERBB信號的複雜性，並描繪了關鍵的微環境細胞和發育中的腸道信號。
據悉，人類腸道幹細胞的微環境促進自我更新和上皮功能，但對其發育了解甚少。
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