A5035946828- Cancer Cells and Metastasis
- Digestive system and related health
- Tissue Engineering and Regenerative Medicine
- Cancer-related gene regulation
- Fibroblast Growth Factor Research
- Congenital Diaphragmatic Hernia Studies
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Cancer-related molecular mechanisms research
Dana-Farber Cancer Institute
2021-2023
Harvard University
2022
Abstract PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, organoid assays identify regional subpopulations supportive capacities of purified mouse corpus antral PDGFRA + Sub-epithelial Hi myofibroblasts principal sources BMP ligands two...
Barrett's esophagus (BE) and gastric intestinal metaplasia are related premalignant conditions in which areas of human stomach epithelium express mixed features. Intestinal transcription factors (TFs) expressed both conditions, with unclear causal roles cis-regulatory mechanisms. Ectopic CDX2 reprogrammed isogenic mouse organoid lines to a hybrid stomach-intestinal state transcriptionally similar clinical metaplasia; squamous esophageal organoids resisted this CDX2-mediated effect....
Wnt and Rspondin (RSPO) signaling drives proliferation, 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 smooth muscle cell populations. Diverse sub-cryptal provide redundant supportive factors, with certain BMPi most potent co-factor, RSPO2, restricted to single types. Niche functions refine during critical period...
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 dependencies but structurally distinct from intestine each other. Previous studies considered antrum as whole did not assess functions. Using high-resolution imaging sequencing, we identify regional subpopulations properties of purified mouse PDGFRA
Summary Wnt and Rspondin (RSPO) signaling drives proliferation, 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 smooth muscle cell populations. Diverse sub-cryptal provide redundant supportive factors, with certain BMPi most potent co-factor, RSPO2, restricted to single types. Niche functions refine during critical period...