Publications by authors named "Miho Koizumi"
Article Synopsis
- The genome faces constant DNA damage from both internal and external sources, requiring precise regulation of repair mechanisms to maintain integrity.
- After exposure to ionizing radiation (IR), the modification of histone H3 (H3K4me3) shows a decrease shortly after and an increase later, indicating the dynamic response of chromatin to DNA damage in both human and mouse cells.
- PTIP, a critical component of a histone methyltransferase complex, is necessary for the upregulation of H3K4me3 and helps induce cell cycle arrest by activating the PRDM1 cell cycle inhibitor, with its reduced expression linked to acute myeloid leukemia.
Article Synopsis
- - The study investigates reserve cells in the gastrointestinal tract, focusing on their ability to regenerate after tissue damage and whether they exist as long-term resting cells.
- - Researchers found a population of long-term slow-cycling cells in the gastric corpus, specifically a subpopulation of chief cells, that show unique markers associated with cellular stress and regeneration.
- - Inducing damage to the gastric mucosa with indomethacin causes these quiescent cells to proliferate, suggesting they play a crucial role in stomach regeneration.
MBTD1 preserves adult hematopoietic stem cell pool size and function.
Proc Natl Acad Sci U S A
August 2023
Article Synopsis
- - The study investigates the role of MBTD1, a protein important in hematopoietic stem cells (HSCs), showing it is vital for maintaining HSC quantity and functionality, particularly in fetal development.
- - Researchers created conditional knockout mice to explore MBTD1's influence on adult HSCs, finding that its absence led to increased HSC numbers but caused defects in stress response and cell cycle regulation.
- - The findings suggest that MBTD1 helps maintain the quiescence of HSCs by interacting with the FOXO3a protein; restoring FOXO3a in deficient HSCs corrected the observed abnormalities, establishing MBTD1 as key in regulating HSC pool size and health.
Recent studies have demonstrated that epigenetic modifications are deeply involved in neurogenesis; however, the precise mechanisms remain largely unknown. To determine the role of UTX (also known as KDM6A), a demethylase of histone H3K27, in neural development, we generated Utx-deficient mice in neural stem/progenitor cells (NSPCs). Since Utx is an X chromosome-specific gene, the genotypes are sex-dependent; female mice lose both Utx alleles (Utx ), and male mice lose one Utx allele yet retain one Uty allele, the counterpart of Utx on the Y chromosome (Utx ).
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- Detailed analysis shows that genetic rearrangements of chromosome 3 drive certain myeloid leukemias by increasing EVI1 transcription through enhancer changes.
- A novel EVI1 RNA variant, created by mutations in the splicing factor SF3B1, contributes to acute myeloid leukemia transformation and is frequently found in these patients.
- Mutant SF3B1 promotes abnormal EVI1 splicing, enhancing stem cell self-renewal and accelerating leukemia development in mouse models, highlighting a crucial link between splicing mutations and myeloid leukemia pathogenesis.
Epigenetic regulation is essential for the maintenance of the hematopoietic system, and its deregulation is implicated in hematopoietic disorders. In this study, UTX, a demethylase for lysine 27 on histone H3 (H3K27) and a component of COMPASS-like and SWI/SNF complexes, played an essential role in the hematopoietic system by globally regulating aging-associated genes. Utx-deficient (UtxΔ/Δ) mice exhibited myeloid skewing with dysplasia, extramedullary hematopoiesis, impaired hematopoietic reconstituting ability, and increased susceptibility to leukemia, which are the hallmarks of hematopoietic aging.
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- Epigenetic deregulation, specifically through mutations in KDM6A, plays a crucial role in bladder cancer development, but the underlying mechanisms remain poorly understood.
- Researchers created genetically modified mice to study the effects of KDM6A deficiency in conjunction with the tumor-promoting agent BBN, analyzing various molecular and cellular aspects of bladder cancer.
- Their results showed that KDM6A deficiency activates inflammatory pathways and promotes cancer characteristics, suggesting that targeted therapies against specific molecules could be effective for treating bladder cancer linked to KDM6A dysfunction.