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Transl. Med."],"published-print":{"date-parts":[[2026,3,25]]},"abstract":"<jats:p>\n                    Congenital dyserythropoietic anemia type II (CDAII) is an autosomal recessive disease resulting from loss-of-function mutations in\n                    <jats:italic toggle=\"yes\">SEC23 homolog B<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">SEC23B<\/jats:italic>\n                    ). We have previously shown that increased expression of SEC23A, a paralogous protein for SEC23B, rescues the CDAII erythroid defect. Here, we generated a human erythroid cell line that expresses enhanced green fluorescent protein (eGFP) from the endogenous\n                    <jats:italic toggle=\"yes\">SEC23A<\/jats:italic>\n                    locus and performed a small-molecule screen to identify compounds that increased SEC23A-eGFP abundance. The top compound passing all filters was an inhibitor of lysine-specific demethylase 1 (LSD1). We found that LSD1 inhibition with RN1 resulted in increased SEC23A expression in erythroid cells derived from human hematopoietic stem and progenitor cells (HSPCs) at doses that did not impair erythroid cell growth or differentiation and rescued the erythroid defect resulting from\n                    <jats:italic toggle=\"yes\">SEC23B<\/jats:italic>\n                    deletion. Genetic down-regulation of\n                    <jats:italic toggle=\"yes\">LSD1<\/jats:italic>\n                    led to a marked increase in\n                    <jats:italic toggle=\"yes\">SEC23A<\/jats:italic>\n                    mRNA expression in HSPC-derived erythroid cells. Deletion of\n                    <jats:italic toggle=\"yes\">Lsd1<\/jats:italic>\n                    in mouse erythroid cells resulted in increased\n                    <jats:italic toggle=\"yes\">Sec23a<\/jats:italic>\n                    expression, and RN1 treatment ameliorated the erythroid defect observed in a CDAII mouse model. Mechanistically, we found that LSD1 occupied a sequence in the\n                    <jats:italic toggle=\"yes\">SEC23A<\/jats:italic>\n                    promoter, repressing\n                    <jats:italic toggle=\"yes\">SEC23A<\/jats:italic>\n                    transcription. Deletion of the promotor sequence occupied by LSD1 resulted in increased SEC23A expression and amelioration of CDAII. These findings highlight that LSD1 represses\n                    <jats:italic toggle=\"yes\">SEC23A<\/jats:italic>\n                    transcription and that LSD1 inhibition results in de-repression of\n                    <jats:italic toggle=\"yes\">SEC23A<\/jats:italic>\n                    expression and amelioration of the CDAII erythroid defect, suggesting promising therapeutic strategies for CDAII.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adt4859","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:58:21Z","timestamp":1774461501000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["LSD1 inhibition ameliorates congenital dyserythropoietic anemia type II"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4897-1265","authenticated-orcid":true,"given":"Lei","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0519-8776","authenticated-orcid":true,"given":"Richard","family":"King","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2810-8091","authenticated-orcid":true,"given":"Greggory","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-6278","authenticated-orcid":true,"given":"Kaiwen","family":"Deng","sequence":"additional","affiliation":[{"name":"Computational and Medical Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-7164","authenticated-orcid":true,"given":"Beth","family":"McGee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4915-4038","authenticated-orcid":true,"given":"Ann","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1062-6774","authenticated-orcid":true,"given":"Ginette","family":"Balbin-Cuesta","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zesen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Drysdale","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph C.","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Kerpet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanfang","family":"Guan","sequence":"additional","affiliation":[{"name":"Computational and Medical Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-4258","authenticated-orcid":true,"given":"Ayse Bilge","family":"Ozel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-9641","authenticated-orcid":true,"given":"Aaron","family":"Robida","sequence":"additional","affiliation":[{"name":"Center for Chemical Genomics, Life Sciences Institute, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-1825","authenticated-orcid":true,"given":"James Douglas","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-5953","authenticated-orcid":true,"given":"Rami","family":"Khoriaty","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA."},{"name":"University of Michigan Rogel Cancer Center, Ann Arbor, MI 48109, 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