{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:09:23Z","timestamp":1778875763263,"version":"3.51.4"},"reference-count":84,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DOD","award":["W81XWH2110148"],"award-info":[{"award-number":["W81XWH2110148"]}]},{"DOI":"10.13039\/100008884","name":"Edward P. 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FA genes have a role in suppressing DNA-RNA hybrids, termed R-loops, which can be generated via transcription mediated by RNA polymerase (RNAP). How these processes, including a role in fate determination of hematopoietic stem cells (HSCs), are related to BMF is largely unknown. Single FA gene KO in mice does not recapitulate most phenotypes observed in patients with FA. Thus, we generated a mouse model for FA by introducing heterozygous\n                    <jats:italic>Setd2<\/jats:italic>\n                    , which restricts RNAP-dependent transcription. We showed that FA patient\u2013derived cells and\n                    <jats:italic>\n                      Setd2\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                      Fanca\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    HSCs share increased R-loop and dsRNA levels and a ribosomal biogenesis defect. Further,\n                    <jats:italic>\n                      Setd2\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                      Fanca\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    HSCs displayed cell cycle arrest, mitotic errors, and BMF phenotypes. Importantly, utilizing our\n                    <jats:italic>\n                      Setd2\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                      Fanca\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice, we discovered that Juglone, a pan-RNAP inhibitor, reduces R-loop and dsRNA and reverses ribosomal biogenesis defects and mitotic errors, thereby rescuing BMF. This study establishes a mouse model that underscores a key role for R-loop formation, ribosomal biogenesis defects, and mitotic errors in HSCs in driving BMF in FA. We also introduce a potential therapeutic avenue based upon pan-inhibition of RNAPs utilizing Juglone.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.192126","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:00:46Z","timestamp":1775584846000},"source":"Crossref","is-referenced-by-count":0,"title":["Insights and modulation of RNA polymerase\u2013dependent R-loop and dsRNA in Fanconi anemia hematopoietic stem cells"],"prefix":"10.1172","volume":"11","author":[{"given":"Michihiro","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas, USA."},{"name":"Department of Pathology and Laboratory Medicine, UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA."},{"name":"Mays Cancer Center at UT Health San Antonio, San Antonio, Texas, USA."},{"name":"Laboratory of Stem Cell Engineering, International Research 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