美国丹娜-法伯癌症研究院Ramesh A. Shivdasani研究团队发现，不同的间充质细胞群体产生关键的肠道BMP信号梯度。相关论文于2020年2月20日在线发表在《细胞—干细胞》杂志上。

Title: Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient

Author: Neil McCarthy, Elisa Manieri, Elaine E. Storm, Assieh Saadatpour, Adrienne M. Luoma, Varun N. Kapoor, Shariq Madha, Liam T. Gaynor, Christian Cox, Shilpa Keerthivasan, Kai Wucherpfennig, Guo-Cheng Yuan, Frederic J. de Sauvage, Shannon J. Turley, Ramesh A. Shivdasani

Issue&Volume: 2020-02-20

Abstract: Intestinal stem cells (ISCs) are confined to crypt bottoms and their progeny differentiatenear crypt-villus junctions. Wnt and bone morphogenic protein (BMP) gradients drivethis polarity, and colorectal cancer fundamentally reflects disruption of this homeostaticsignaling. However, sub-epithelial sources of crucial agonists and antagonists thatorganize this BMP gradient remain obscure. Here, we couple whole-mount high-resolutionmicroscopy with ensemble and single-cell RNA sequencing (RNA-seq) to identify threedistinct PDGFRA+ mesenchymal cell types. PDGFRA(hi) telocytes are especially abundant at the villusbase and provide a BMP reservoir, and we identified a CD81+ PDGFRA(lo) population present just below crypts that secretes the BMP antagonistGremlin1. These cells, referred to as trophocytes, are sufficient to expand ISCs in vitro without additional trophic support and contribute to ISC maintenance in vivo. This study reveals intestinal mesenchymal structure at fine anatomic, molecular,and functional detail and the cellular basis for a signaling gradient necessary fortissue self-renewal.

DOI: 10.1016/j.stem.2020.01.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30008-4