Identification of Transcription factors in brown adipose cell differentiation by single-nucleus chromatin analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16102
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: NAKAMURA MASAHIRO 東京大学, 大学院工学系研究科(工学部), 特任助教 (40634449)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: クロマチン / シングルセル / 遺伝子発現

Outline of Final Research Achievements

In this study, we analyzed single-nucleus chromatin structure and single-nucleus expression at each stage of differentiation from brown fat precursor cells to brown fat cells. First, we used these gene expression changes as indicators to identify chromatin structural changes, which led to the identification of novel transcription factors, and then we attempted to elucidate the relationship between these novel transcription factors and chromatin structural changes. First, we were able to identify gene expression specific to each stage of differentiation. We identified open chromatin regions at each stage of differentiation from brown adipose progenitor cells to brown adipocytes on a cell-by-cell basis using an improved version of ATAC-seq. We identified open chromatin regions specific to each stage of differentiation and found that transcription factor motifs are enriched in these regions.

Free Research Field

エピゲノム研究

Academic Significance and Societal Importance of the Research Achievements

本研究では、褐色脂肪前駆細胞から褐色脂肪細胞への分化各段階におけるシングル核クロマチン構造解析及びシングル核発現解析を行い、褐色脂肪細胞分化を促進させる新規転写因子を同定し、新規転写因子が褐色脂肪細胞のクロマチン構造をどう変化させうるのかを、少数細胞を用いたChIP-seq解析およびシングルセル発現解析を用いることによって明らかにすることを目的とした。褐色脂肪細胞分化をモデルケースとして、転写因子のオンオフやエピゲノム変化が分化関連遺伝子の発現に影響を及ぼし、さらなるエピゲノム変化を引き起こして分化を制御している過程をの一部を詳細に示すことができた。