Usage Information
Abstract
Fanconi anemia (FA) is the most common BM failure (BMF) syndrome. 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 Setd2, which restricts RNAP-dependent transcription. We showed that FA patient–derived cells and Setd2+/– Fanca–/– HSCs share increased R-loop and dsRNA levels and a ribosomal biogenesis defect. Further, Setd2+/– Fanca–/– HSCs displayed cell cycle arrest, mitotic errors, and BMF phenotypes. Importantly, utilizing our Setd2+/– Fanca–/– 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.
Authors
Michihiro Hashimoto, Xiaomin Feng, Jie Bai, Huimin Zeng, Tian Li, Jue Li, Terumasa Umemoto, Paul R. Andreassen, Gang Huang
Usage data is cumulative from February 2026 through August 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,518 | 0 |
| 487 | 0 | |
| Figure | 727 | 0 |
| Table | 118 | 0 |
| Supplemental data | 251 | 0 |
| Citation downloads | 320 | 0 |
| Totals | 3,421 | 0 |
| Total Views | 3,421 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
