| Literature DB >> 32693086 |
Thierry Jardé1, Wing Hei Chan2, Fernando J Rossello3, Tanvir Kaur Kahlon2, Mandy Theocharous4, Teni Kurian Arackal2, Tracey Flores2, Mégane Giraud2, Elizabeth Richards2, Eva Chan2, Genevieve Kerr2, Rebekah M Engel5, Mirsada Prasko2, Jacqueline F Donoghue6, Shin-Ichi Abe7, Toby J Phesse8, Christian M Nefzger9, Paul J McMurrick10, David R Powell11, Roger J Daly4, Jose M Polo12, Helen E Abud13.
Abstract
Epidermal growth factor (EGF) maintains intestinal stem cell (ISC) proliferation and is a key component of organoid growth media yet is dispensable for intestinal homeostasis, suggesting roles for multiple EGF family ligands in ISC function. Here, we identified neuregulin 1 (NRG1) as a key EGF family ligand that drives tissue repair following injury. NRG1, but not EGF, is upregulated upon damage and is expressed in mesenchymal stromal cells, macrophages, and Paneth cells. NRG1 deletion reduces proliferation in intestinal crypts and compromises regeneration capacity. NRG1 robustly stimulates proliferation in crypts and induces budding in organoids, in part through elevated and sustained activation of mitogen-activated protein kinase (MAPK) and AKT. Consistently, NRG1 treatment induces a proliferative gene signature and promotes organoid formation from progenitor cells and enhances regeneration following injury. These data suggest mesenchymal-derived NRG1 is a potent mediator of tissue regeneration and may inform the development of therapies for enhancing intestinal repair after injury.Entities:
Keywords: EGF; ERBB3; PDGFRα+ stromal cells; cell proliferation; intestinal stem cells; macrophages; neuregulin 1; niche; stem cell identity; tissue regeneration
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Year: 2020 PMID： 32693086 DOI： 10.1016/j.stem.2020.06.021
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633