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While the microenvironment that supports extramedullary hematopoiesis response has gained interest, a niche for splenic HSCs at steady-state remains undescribed. Here, we have uncovered a red-pulp-specific, myofibroblastic niche that supports murine splenic HSCs within a\u2009\u2248\u2009200-\u03bcm-wide capsular zone. Detailed spatial-distribution and perturbation analysis showed the importance of myofibroblasts in maintaining HSCs in a quiescent state. Unlike reported for the adult bone marrow, the HSCs in splenic niche were not spatially associated with vascular components. G-CSF-mediated chemokine alteration and 5-FU-induced proliferation resulted in HSCs shifts away from the splenic capsule. Interestingly, upon regaining quiescence, the HSCs re-occupied niches close to capsular myofibroblasts. Proteomic interactome profiles confirmed the relevance of capsular myofibroblasts for splenic HSCs and identified potential niche regulators of HSC maintenance. Together, this study demonstrates a dynamic HSC localization in the spleen and its niche context at homeostasis and under stress. It offers a model to uncover novel regulators crucial for HSC function.<\/jats:p>","DOI":"10.1038\/s44318-025-00477-2","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T10:00:38Z","timestamp":1749117638000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A capsular myofibroblastic niche maintains hematopoietic stem cells in the spleen"],"prefix":"10.1038","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4869-848X","authenticated-orcid":false,"given":"Shubham Haribhau","family":"Mehatre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7268-4750","authenticated-orcid":false,"given":"Sreelakshmi","family":"Sanam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5024-1535","authenticated-orcid":false,"given":"Harsh","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2510-5242","authenticated-orcid":false,"given":"Amulya V","family":"Hejjaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhila S","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-0691","authenticated-orcid":false,"given":"Mohammad Tauqeer","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5176-1510","authenticated-orcid":false,"given":"Satish","family":"Khurana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"477_CR1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nature15250","volume":"526","author":"M Acar","year":"2015","unstructured":"Acar M, Kocherlakota KS, Murphy MM, Peyer JG, Oguro H, Inra CN, Jaiyeola C, Zhao Z, Luby-Phelps K, Morrison SJ (2015) Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. 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