{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:38:54Z","timestamp":1792417134011,"version":"4.4.0"},"reference-count":75,"publisher":"American Society of Hematology","issue":"1","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,14]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Megakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)\/CXCL4. Here, we show that the intra-\u03b1-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN\u2013\/\u2013 MKs released \u223c80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in\u00a0vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)\/protein interactions. In\u00a0vivo, SRGN\u2013\/\u2013 mice had an interstitial accumulation of PF4, transforming growth factor \u03b21, interleukin-1\u03b2, and tumor necrosis factor \u03b1 in their bone marrow and increased numbers of immature MKs, consistent with their mild thrombocytopenia. SRGN\u2013\/\u2013 mice also had reduced numbers of hematopoietic stem cells and multipotent progenitors, reduced laminin, and increased collagen I deposition. These findings demonstrate that MKs depend on SRGN and its charged GAGs to balance the distribution of PF4 and perhaps other factors between their \u03b1-granules and their adjacent extracellular spaces. Disrupting this balance negatively affects MK development and bone marrow microenvironment homeostasis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/bloodadvances.2024012995","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T19:00:19Z","timestamp":1719601219000},"page":"15-28","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Serglycin controls megakaryocyte retention of platelet factor 4 and influences megakaryocyte fate in bone marrow"],"prefix":"10.1182","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9276-0092","authenticated-orcid":false,"given":"Joshua","family":"Lykins","sequence":"first","affiliation":[{"name":"1Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2725-8493","authenticated-orcid":false,"given":"Isabelle C.","family":"Becker","sequence":"additional","affiliation":[{"name":"2Department of Surgery, Boston Children\u2019s Hospital, Boston, MA"},{"name":"3Department of Surgery, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Camacho","sequence":"additional","affiliation":[{"name":"2Department of Surgery, Boston Children\u2019s Hospital, Boston, MA"},{"name":"3Department of Surgery, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-4367","authenticated-orcid":false,"given":"Hammodah R.","family":"Alfar","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoonWoo","family":"Park","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6547-9663","authenticated-orcid":false,"given":"Joseph","family":"Italiano","sequence":"additional","affiliation":[{"name":"2Department of Surgery, Boston Children\u2019s Hospital, Boston, MA"},{"name":"3Department of Surgery, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5577-0473","authenticated-orcid":false,"given":"Sidney W.","family":"Whiteheart","sequence":"additional","affiliation":[{"name":"1Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, 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