Data from: Identification of ZEB1 as a central component of the adipogenic gene regulatory network

Adipose tissue is a key determinant of whole body metabolism and energy homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective. Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the C/EBP protein family and the master regulator PPARγ. To elucidate further components of the adipogenic gene regulatory network, we performed a large-scale transcription factor (TF) screen overexpressing 734 TFs in mouse pre-adipocytes and probed their effect on differentiation. We identified 23 novel pro-adipogenic TFs and characterized the top ranking TF, ZEB1, as being essential for adipogenesis both in vitro and in vivo. Moreover, its expression levels correlate with fat cell differentiation potential in humans. Genomic profiling further revealed that this TF directly targets and controls the expression of most early and late adipogenic regulators, identifying ZEB1 as a central transcriptional component of fat cell differentiation.脂肪组织（adipose tissue）是决定全身代谢与能量稳态的关键因素。因此，从生物医学视角解析脂肪生成（adipogenesis）背后的调控机制具有重要研究价值。目前学界对脂肪细胞分化的认知，主要聚焦于由CCAAT增强子结合蛋白（C/EBP）家族与核心调控因子过氧化物酶体增殖物激活受体γ（PPARγ）驱动的转录级联反应。为阐明脂肪生成基因调控网络的更多组成部分，我们开展了大规模转录因子（transcription factor, TF）筛选实验：在小鼠前脂肪细胞中过表达734种转录因子，并检测其对脂肪细胞分化的影响。本研究共鉴定出23种新型促脂肪生成转录因子，并对排名首位的ZEB1进行了功能表征，证实其在体外与体内均为脂肪生成所必需。此外，ZEB1的表达水平与人类脂肪细胞的分化潜能显著相关。基因组谱分析进一步揭示，该转录因子可直接靶向并调控绝大多数早期与晚期脂肪生成调控因子的表达，从而确认ZEB1是脂肪细胞分化的核心转录组分。