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However, the role of ferroptosis in stem cells has not yet been investigated. Glutathione peroxidase 4 (GPX4) is a critical suppressor of lipid peroxidation and ferroptosis. Here, we study the function of GPX4 and ferroptosis in hematopoietic stem and progenitor cells (HSPCs) in mice with\n                    <jats:italic>Gpx4<\/jats:italic>\n                    deficiency in the hematopoietic system. We find that\n                    <jats:italic>Gpx4<\/jats:italic>\n                    deletion solely in the hematopoietic system has no significant effect on the number and function of HSPCs in mice. Notably, hematopoietic stem cells (HSCs) and hematopoietic progenitor cells lacking\n                    <jats:italic>Gpx4<\/jats:italic>\n                    accumulated lipid peroxidation and underwent ferroptosis in vitro. \u03b1-Tocopherol, the main component of vitamin E, was shown to rescue the\n                    <jats:italic>Gpx<\/jats:italic>\n                    4-deficient HSPCs from ferroptosis in vitro. When\n                    <jats:italic>Gpx4<\/jats:italic>\n                    knockout mice were fed a vitamin E-depleted diet, a reduced number of HSPCs and impaired function of HSCs were found. Furthermore, increased levels of lipid peroxidation and cell death indicated that HSPCs undergo ferroptosis. Collectively, we demonstrate that GPX4 and vitamin E cooperatively maintain lipid redox balance and prevent ferroptosis in HSPCs.\n                  <\/jats:p>","DOI":"10.1038\/s41419-021-04008-9","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:03:18Z","timestamp":1626307398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":203,"title":["GPX4 and vitamin E cooperatively protect hematopoietic stem and progenitor cells from lipid peroxidation and ferroptosis"],"prefix":"10.1038","volume":"12","author":[{"given":"Qian","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexian","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanlong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8099-6327","authenticated-orcid":false,"given":"Junxia","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-0003","authenticated-orcid":false,"given":"Fudi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"4008_CR1","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.cell.2008.01.025","volume":"132","author":"SH Orkin","year":"2008","unstructured":"Orkin SH, Zon LI. 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