2019 Fiscal Year Final Research Report
Role of genomic imprinting in the establishment of ESCs
| Project/Area Number |
16H06223
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | ES細胞 / 未分化性 / DNAメチル化 / インプリンティング |
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| Outline of Final Research Achievements |
Embryonic stem (ES) cells, which can maintain almost infinite pluripotency, are established by the culture of internal cell mass (ICM) of blastocyst that appear transiently in the very early stages of development. The molecular mechanism how cells in an internal cell mass, which is destined to differentiate in a few days in vivo, acquire the ability to maintain undifferentiated state permanently has remained unexplored. In this project, we focused on the culture condition affecting the state of genome imprinting, which is a mechanism of single-allele gene expression. As a result, we succeeded in establishing a novel method for the establishment and culture of ES cells that minimizes the use of MEK inhibitors that induce genome-wide DNA demethylation.
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| Free Research Field |
発生生物学
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| Academic Significance and Societal Importance of the Research Achievements |
胚性幹細胞（ES細胞）は基礎・応用両方において広く用いられている。特に、高い遺伝的恒常性を活かし、スクリーニングや発生分化研究に汎用されている。しかし、近年用いられている培養条件では、DNAのメチル化状態がゲノム全体で低下し、生体内の胚のエピジェネティック状態を反映していないことが問題となっていた。本研究成果で報告された新規のES細胞樹立、培養法はこの問題を解決できる可能性が高い。また、永続的な未分化性の獲得は細胞のがん化とも共通する変化が認められる。本研究成果は、未分化性維持機構の解明のみならず、将来的には生体内の細胞の変質、維持の背景にある分子メカニズムの解明に貢献するものと考えている。
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