Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient.

ABSTRACT: Intestinal stem cells (ISCs) are confined to crypt bottoms and their progeny differentiate near crypt-villus junctions. Wnt and bone morphogenic protein (BMP) gradients drive this polarity, and colorectal cancer fundamentally reflects disruption of this homeostatic signaling. However, sub-epithelial sources of crucial agonists and antagonists that organize this BMP gradient remain obscure. Here, we couple whole-mount high-resolution microscopy with ensemble and single-cell RNA sequencing (RNA-seq) to identify three distinct PDGFRA⁺ mesenchymal cell types. PDGFRA(hi) telocytes are especially abundant at the villus base and provide a BMP reservoir, and we identified a CD81⁺ PDGFRA(lo) population present just below crypts that secretes the BMP antagonist Gremlin1. These

SUBMITTER: McCarthy N 

PROVIDER: S-EPMC7412576 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature