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2022 Fiscal Year Final Research Report

Enhancer based fine-tuning of Runx family for the regulation of HSC division during bone marrow recovery

Research Project

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Project/Area Number 21K16272
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKumamoto University

Principal Investigator

Ahmad Shah Adil Ishtiyaq  熊本大学, 国際先端医学研究機構, 客員助教 (80893833)

Project Period (FY) 2021-04-01 – 2023-03-31
Keywordsstem cells
Outline of Final Research Achievements

I compared chromatin accessibility of Runx enhancers between self-renewal and differentiation types of HSCs after 5-FU administration by ATA-seq, and identified candidate regions of novel metabolic-epigenetic functional axis targeting RUNX enhancer sequences. Moreover, I confirm that these regions have H3K27 acetylation by CUT&Tag system. In addition, Runx3, which is related to differentiation, was highly expressed in EPCR Low HSCs, compared to EPCR High HSCs that is most primitive HSCs. Consistent with this results, the chromatin accessibility of enhancer regions that I identify by using HSCs obtained from 5-FU-treated mice was enhanced when EPCR high HSCs differentiate into EPCR low HSCs in vitro. These data suggest that I identify the enhancer regions of Runx3 that is important for the regulation of expression level in HSCs and this enhancer regions is involved in the differentiation of HSCs.

Free Research Field

Hematology

Academic Significance and Societal Importance of the Research Achievements

The achievement of my research may contribute to understanding the mechanism for the determination of HSC fate under proliferation conditions. So, this achievement may also contribute to the development for ex vivo expansion of HSCs.

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Published: 2024-01-30  

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