{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:31Z","timestamp":1792788571978,"version":"4.5.0"},"reference-count":41,"publisher":"The Company of Biologists","issue":"18","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institutes of Health","award":["R01DK121540"],"award-info":[{"award-number":["R01DK121540"]}]},{"name":"National Institutes of Health","award":["K01DK125639"],"award-info":[{"award-number":["K01DK125639"]}]},{"name":"North Carolina State University","id":[{"id":"https:\/\/ror.org\/04tj63d06","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>When intestinal stem cells (ISCs) are damaged, other epithelial cells de-differentiate to restore the ISC compartment. Immune, nerve and lymphatic endothelial cells contribute signals that promote this response, but it is unclear whether or how the native mesenchymal niche senses and responds to ISC loss. In homeostasis, trophocytes and smooth muscle beneath intestinal crypts secrete BMP inhibitors (BMPi) and R-spondins to foster ISC self-renewal, whereas sub-epithelial myofibroblasts (SEMFs) concentrated at crypt tops promote differentiation through bone morphogenetic proteins (BMPs). We assessed transcriptional responses in mouse sub-epithelial populations after ablating ISCs with whole-body irradiation and treating Lgr5DTR mice with diphtheria toxin. More than any other cell type, SEMFs modulated expression of genes related to ISC expansion. However, the BMPi gene Smoc1 and non-canonical Wnt signals, both expressed in SEMFs after whole-body irradiation, were dispensable for ISC restoration. Instead, SEMFs appear to support ISC regeneration through factors that are not induced by ISC attrition per se but by local inflammation. These findings reveal unexpectedly limited transcriptional modulation of the native niche after ISC losses and context-dependent signaling functions for SEMFs.<\/jats:p>","DOI":"10.1242\/dev.205629","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:23:56Z","timestamp":1790605436000},"source":"Crossref","is-referenced-by-count":0,"title":["Subepithelial myofibroblasts enhance stem cell regeneration after intestinal epithelial damage"],"prefix":"10.1242","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6021-1369","authenticated-orcid":false,"given":"Neil","family":"McCarthy","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, North Carolina State University 1 Department of Molecular Biomedical Sciences , , Raleigh, NC 27502 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2838-3537","authenticated-orcid":false,"given":"Camila Mendez","family":"Jimenez","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, North Carolina State University 1 Department of Molecular Biomedical Sciences , , Raleigh, NC 27502 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Tie","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute 2 Department of Medical Oncology and Center for Functional Cancer Epigenetics , , Boston, MA 02215 ,","place":["USA"]},{"name":"Harvard Medical School 3 Department of Medicine , , Boston, MA, 02215 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-8469","authenticated-orcid":false,"given":"Gizelle","family":"McCarthy","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, North Carolina State University 1 Department of Molecular Biomedical Sciences , , Raleigh, NC 27502 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6022-6560","authenticated-orcid":false,"given":"Shariq","family":"Madha-Krause","sequence":"additional","affiliation":[{"name":"Harvard Medical School 3 Department of Medicine , , Boston, MA, 02215 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8215-8439","authenticated-orcid":false,"given":"Ruiyang","family":"He","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute 2 Department of Medical Oncology and Center for Functional Cancer Epigenetics , , Boston, MA 02215 ,","place":["USA"]},{"name":"Harvard Medical School 3 Department of Medicine , , Boston, MA, 02215 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh A.","family":"Shivdasani","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute 2 Department of Medical Oncology and Center for Functional Cancer Epigenetics , , Boston, MA 02215 ,","place":["USA"]},{"name":"Harvard Medical School 3 Department of Medicine , , Boston, MA, 02215 ,","place":["USA"]},{"name":"Harvard Stem Cell Institute 4 , Cambridge, MA 02139 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"2026092810235051700_DEV205629C1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/s41586-019-1154-y","article-title":"Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell","volume":"569","author":"Ayyaz","year":"2019","journal-title":"Nature"},{"key":"2026092810235051700_DEV205629C2","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. 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