Biology subjects

Tie, G.

Publications and source records attributed to Tie, G..

2 recordsLinked to original sources

bioRxiv2023

Structure, signals, and cellular elements of the mouse gastric mesenchymal niche

PDGFRA-expressing mesenchyme provides a niche for intestinal stem cells. Corresponding compartments are unknown in the stomach, where corpus and antral glandular epithelia have similar niche dependencies but are structurally distinct from the intestine and from each other. Previous studies considered antrum and corpus as a whole and did not assess niche functions. Using high-resolution imaging and sequencing, we identify regional subpopulations and niche properties of purified mouse corpus and antral PDGFRA+ cells. PDGFRAHi sub-epithelial myofibroblasts are principal sources of BMP ligands in both gastric segments; two molecularly distinct groups distribute asymmetrically along antral glands but together fail to support epithelial organoids in vitro. In contrast, strategically positioned PDGFRALo cells that express CD55 enable corpus and antral organoid growth in the absence of other cellular or soluble factors. Our study provides detailed insights into spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for stem cell support.

cell biology↗

bioRxiv2021

Birth and delineation of the intestinal stem cell niche

Wnt and Rspondin (RSPO) signaling drives proliferation, and bone morphogenetic protein inhibitors (BMPi) impede differentiation, of intestinal stem cells (ISCs). Here we identify the adult mouse ISC niche as a complex, multi-layered structure that encompasses distinct mesenchymal and smooth muscle cell populations. Diverse sub-cryptal cells provide redundant supportive factors, with certain BMPi and the most potent Wnt co-factor, RSPO2, restricted to single cell types. Niche functions refine during a critical period of postnatal crypt morphogenesis, in part to oppose dense aggregation of BMP-expressing sub-epithelial myofibroblasts that promote epithelial differentiation. A specialized muscle layer, the muscularis mucosae, first appears during this period and supplements neighboring RSPO and BMPi sources. In vivo ablation of smooth muscle raises BMP activity and potently limits a pre-weaning burst of crypt fission. Thus, distinct and progressively specialized mesenchymal components together create the milieu required to propagate crypts during rapid organ growth and to sustain adult ISCs.

developmental biology↗