{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:55:53Z","timestamp":1780343753137,"version":"3.54.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Bone marrow (BM) suppression is the most prevalent dose-limiting side effect of chemotherapy and radiotherapy. Exposure to ionizing radiation (IR) results in acute BM suppression and long-term BM injury. Gasdermin E (GSDME) is crucial for mediating apoptosis and pyroptosis during chemotherapy. However, its role in radiation-induced hematopoietic injury is not well established. Therefore, we aimed to investigate the role of GSDME on radiation-induced hematopoietic injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established hematopoietic radiation injury models in C57BL\/6 mice and Gsdme<jats:sup>\u2212\/\u2212<\/jats:sup> mice. The peripheral blood (PB) counts, phenotypes of BM cells and spleen cells were analyzed. The colony-forming unit-granulocyte and macrophage assays and competitive repopulation assays were measured to evaluate the function of hematopoietic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that GSDME regulates the survival and differentiation of hematopoietic stem cells (HSCs). The knockout of GSDME reduced the number and proliferation of HSCs and shortened the survival time of mice post IR. Additionally, GSDME knockout protected LSK (Lin-Sca1+c-kit+) cells, long-term HSCs (LT-HSCs), granulocyte\u2013monocyte progenitors (GMPs), and myeloid cells (M cells) from IR injuries during acute BM suppression. Furthermore, GSDME knockout protected LSK cells, LT-HSCs, GMPs and M cells, alleviated the proliferation inhibition of hematopoietic progenitor cells (HPCs) and exacerbated lymphocyte damage during long-term BM injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GSDME is vital for the survival and differentiation of HSCs, and its absence promotes myeloid-biased differentiation postirradiation. These findings highlight the critical role of GSDME in radiation-induced hematopoietic injury, particularly in the myeloid differentiation of HSCs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1544320","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:08:34Z","timestamp":1743768514000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["GSDME knockout alleviates hematopoietic stem cell irradiation injury and aggravates myeloid-biased differentiation"],"prefix":"10.3389","volume":"13","author":[{"given":"Lulu","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinping","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qidong","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deguan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1667\/rr13887.1","article-title":"Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice","volume":"183","author":"Chang","year":"2015","journal-title":"Radiat. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1186\/s13046-022-02533-9","article-title":"OTUD4-mediated GSDME deubiquitination enhances radiosensitivity in nasopharyngeal carcinoma by inducing pyroptosis","volume":"41","author":"Di","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/s0301-472x(01)00685-3","article-title":"The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on primitive hematopoietic stem cell (PHSC) function and numbers, after chemotherapy","volume":"29","author":"Gardner","year":"2001","journal-title":"Exp. Hematol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/ni.3204","article-title":"The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells","volume":"16","author":"Hou","year":"2015","journal-title":"Nat. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41420-020-00349-0","article-title":"The caspase-3\/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer","volume":"6","author":"Jiang","year":"2020","journal-title":"Cell Death Discov."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e62921","DOI":"10.1371\/journal.pone.0062921","article-title":"The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury","volume":"8","author":"Li","year":"2013","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"6066","DOI":"10.1158\/1078-0432.ccr-18-1478","article-title":"Molecular targeted therapies elicit concurrent apoptotic and GSDME-dependent pyroptotic tumor cell death","volume":"24","author":"Lu","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1016\/0360-3016(94)00430-s","article-title":"Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy","volume":"31","author":"Mauch","year":"1995","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"B9","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.stem.2010.06.014","article-title":"Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis","volume":"7","author":"Mohrin","year":"2010","journal-title":"Cell Stem Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41580-019-0103-9","article-title":"Haematopoietic stem cell activity and interactions with the niche","volume":"20","author":"Pinho","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1038\/s41467-019-09397-2","article-title":"Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation","volume":"10","author":"Rogers","year":"2019","journal-title":"Nat. Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"14128","DOI":"10.1038\/ncomms14128","article-title":"Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic\/pyroptotic cell death","volume":"8","author":"Rogers","year":"2017","journal-title":"Nat. Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.1182\/blood-2013-07-515619","article-title":"Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner","volume":"123","author":"Shao","year":"2014","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2021.12.034","article-title":"Radiosensitivity of colorectal cancer and radiation-induced gut damages are regulated by gasdermin E","volume":"529","author":"Tan","year":"2022","journal-title":"Cancer Lett."},{"key":"B15","first-page":"101","article-title":"Long-term bone marrow damage in experimental systems and in patients after radiation or chemotherapy","volume":"5","author":"Testa","year":"1985","journal-title":"Anticancer Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1182\/blood.v92.6.1950","article-title":"Granulocyte colony-stimulating factor enhances bone marrow stem cell damage caused by repeated administration of cytotoxic agents","volume":"92","author":"van Os","year":"1998","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1177\/00220345211073072","article-title":"GSDME is related to prognosis and response to chemotherapy in oral cancer","volume":"101","author":"Wang","year":"2022","journal-title":"J. Dent. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature22393","article-title":"Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin","volume":"547","author":"Wang","year":"2017","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1182\/blood-2005-04-1418","article-title":"Total body irradiation selectively induces murine hematopoietic stem cell senescence","volume":"107","author":"Wang","year":"2006","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1016\/j.bbrc.2017.11.156","article-title":"GSDME mediates caspase-3-dependent pyroptosis in gastric cancer","volume":"495","author":"Wang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41419-019-1441-4","article-title":"Cleavage of GSDME by caspase-3 determines lobaplatin-induced pyroptosis in colon cancer cells","volume":"10","author":"Yu","year":"2019","journal-title":"Cell Death Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1007\/s10495-019-01515-1","article-title":"Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3\/GSDME activation","volume":"24","author":"Zhang","year":"2019","journal-title":"Apoptosis"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1544320\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:08:46Z","timestamp":1743768526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1544320\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,4]]},"references-count":22,"alternative-id":["10.3389\/fcell.2025.1544320"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1544320","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,4]]},"article-number":"1544320"}}