{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:20:45Z","timestamp":1791354045585,"version":"4.3.1"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T00:00:00Z","timestamp":1390262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p>Nrf2 is a major transcriptional activator of cytoprotective genes against oxidative\/electrophilic stress, and Keap1 negatively regulates Nrf2. Emerging works have also suggested a role for Nrf2 as a regulator of differentiation in various cells, but the contribution of Nrf2 to the differentiation of hematopoietic stem cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s) remains elusive. Clarifying this point is important to understand Nrf2 functions in the development and\/or resolution of inflammation. Here, we established two transgenic reporter mouse lines that allowed us to examine Nrf2 expression precisely in <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s. <jats:italic>Nrf2<\/jats:italic> was abundantly transcribed in <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s, but its activity was maintained at low levels due to the Keap1\u2010mediated degradation of Nrf2 protein. When we characterized <jats:italic>Keap1\u2010<\/jats:italic>deficient mice, their bone marrow cells showed enhanced granulocyte\u2010monocyte differentiation at the expense of erythroid and lymphoid differentiation. Importantly, <jats:italic>Keap1<\/jats:italic>\u2010null <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s showed lower expression of erythroid and lymphoid genes than did control <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s, suggesting granulocyte\u2010monocyte lineage priming in <jats:italic>Keap1<\/jats:italic>\u2010null <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s. This abnormal lineage commitment was restored by a concomitant deletion of <jats:italic>Nrf2<\/jats:italic>, demonstrating the Nrf2\u2010dependency of the skewing. Analysis of <jats:italic>Nrf2<\/jats:italic>\u2010deficient mice revealed that the physiological level of Nrf2 is sufficient to contribute to the lineage commitment. This study unequivocally shows that the Keap1\u2010Nrf2 system regulates the cell fate determination of <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s.<\/jats:p>","DOI":"10.1111\/gtc.12126","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T01:49:24Z","timestamp":1390355364000},"page":"239-253","source":"Crossref","is-referenced-by-count":59,"title":["Keap1\u2010Nrf2 system regulates cell fate determination of hematopoietic stem cells"],"prefix":"10.1111","volume":"19","author":[{"given":"Shohei","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry Tohoku University Graduate School of Medicine 2\u20101 Seiryo\u2010machi Aoba\u2010ku Sendai Miyagi 980\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritsuko","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology Tohoku University Graduate School of Medicine 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