Elucidating of transcription factor network during the differentiation of human ES cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15129
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Developmental biology
• Research Institution: Keio University
• Principal Investigator: AKIYAMA TOMOHIKO 慶應義塾大学, 医学部(信濃町), 助教 (20570691)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ES細胞 / 細胞分化 / 転写制御 / クロマチン

Outline of Final Research Achievements

ATAC sequencing was performed to identify open chromatin that regulates differentiation of human ES cells by introduction of transcription factors. Skeletal muscle differentiation by introducing MYOD1 and neuronal differentiation by introducing NGN2 was analysed and we identified several thousands of open chromatin sites specifically present in the differentiated cells. In addition to the sites that MYOD1 and NGN2 originally bind to in adult tissues, there were open chromatin sites that appear specifically when MYOD1 and NGN2 were introduced into ES cells. Together, direct conversions of ES cells to terminally differentiated cells can be achieved by the coordinated action controlled by these two types of open chromatin sites.

Free Research Field

転写制御

Academic Significance and Societal Importance of the Research Achievements

本研究のオープンクロマチン解析では、転写因子ネットワークの変化を詳細に解析することが可能である。個々の転写因子の抗体を用いてゲノム上の転写因子結合サイトを同定する実験では、1500個の転写因子のネットワークを体系的に捉えることができない。オープンクロマチンを調べることにより、細胞分化過程におけるゲノム上の「転写因子結合マップ」を作成することができる。そのため、転写因子ネットワークの全体像が明らかとなり、「幹細胞」と「分化細胞」の違いを生み出す分子基盤を理解できると考えられる。また、新規分化誘導因子が明らかになれば、ES細胞を自在に分化誘導できる革新的技術の開発も期待できる。