Cell子刊:绘制人类肠道生态位发育的转录图谱
  • 利用scRNA-seq和原位验证的方法研究受孕后7-21周的人类肠道发育;
  • 粘膜肌层的平滑肌细胞靠近有增殖能力的隐窝,是WNT和RSPONDIN配体的来源,而EGF在远离隐窝的绒毛上皮中表达;
  • 高表达PDGFRA/F3/DLL1的间充质细胞群沿隐窝-绒毛轴排列,是表皮生长因子家族成员NRG1的来源;
  • 在发育中的肠类培养中,NRG1而不是EGF,通过增加分泌谱系的分化而增加细胞的多样性;
  • 在发育好的肠类培养中,EGF而不是NRG1,支持其增殖和生长。
主编推荐语
爱的抉择
人类肠道干细胞生态位支持上皮细胞的自我更新和功能,但其自身的发育知之甚少。Cell Stem Cell近期发表的文章,利用scRNA-seq和原位验证的方法对受孕后7-21周的人类肠道发育进行研究,表征发育中的人类肠道干细胞生态位中细胞多样性。同时转录组和空间图谱显示,NRG1表达于表皮下间充质细胞中,NRG1而不是EGF促进分泌系细胞的分化,从而增加细胞多样性。研究强调了肠道中EGF/ERBB信号的复杂性,描绘了发育中肠道关键生态位的细胞和信号。
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Cell Stem Cell [IF:20.86]

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

单细胞测序绘制人类肠道生态位发育的图谱

10.1016/j.stem.2020.11.008

2020-12-04, Article

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Abstract:收起
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 with in situ validation approaches to interrogate human intestinal development from 7–21 weeks post conception, assigning molecular identities and spatial locations to cells and factors 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 epidermal growth factor (EGF) family member NEUREGULIN1 (NRG1). In developing intestine enteroid cultures, NRG1, but not EGF, permitted increased cellular diversity via differentiation of secretory lineages. This work highlights the complexities of intestinal EGF/ERBB signaling and delineates key niche cells and signals of the developing intestine.

First Authors:
Emily M Holloway,Michael Czerwinski,Yu-Hwai Tsai

Correspondence Authors:
Jason R Spence

All Authors:
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

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