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从稳健排名聚合分析看小鼠胚胎干细胞成脂分化的转录动力学及关键调控因子

Transcriptional Dynamics and Key Regulators of Adipogenesis in Mouse Embryonic Stem Cells: Insights from Robust Rank Aggregation Analysis.

机构信息

Division of Biology, New York University Abu Dhabi, Saadiyaat Island, Abu Dhabi P.O. Box 129188, United Arab Emirates.

Center for Genomics & Systems Biology, New York University Abu Dhabi, Saadiyaat Island, Abu Dhabi P.O. Box 129188, United Arab Emirates.

出版信息

Int J Mol Sci. 2024 Aug 23;25(17):9154. doi: 10.3390/ijms25179154.

Abstract

Embryonic stem cells are crucial for studying developmental biology due to their self-renewal and pluripotency capabilities. This research investigates the differentiation of mouse ESCs into adipocytes, offering insights into obesity and metabolic disorders. Using a monolayer differentiation approach over 30 days, lipid accumulation and adipogenic markers, such as , , and confirmed successful differentiation. RNA sequencing revealed extensive transcriptional changes, with over 15,000 differentially expressed genes linked to transcription regulation, cell cycle, and DNA repair. This study utilized Robust Rank Aggregation to identify critical regulatory genes like PPARG, CEBPA, and EP300. Network analysis further highlighted , , and as potential key players in adipogenesis and its mature state, validated through RT-PCR. While key adipogenic factors showed plateaued expression levels, suggesting early differentiation events, this study underscores the value of ESCs in modeling adipogenesis. These findings contribute to our understanding of adipocyte differentiation and have significant implications for therapeutic strategies targeting metabolic diseases.

摘要

胚胎干细胞因其自我更新和多能性能力而对发育生物学的研究至关重要。这项研究调查了小鼠胚胎干细胞向脂肪细胞的分化,为肥胖和代谢紊乱提供了深入的了解。使用单层分化方法超过 30 天,脂质积累和脂肪生成标志物,如、、和,证实了分化的成功。RNA 测序揭示了广泛的转录变化,超过 15000 个差异表达基因与转录调控、细胞周期和 DNA 修复有关。这项研究利用稳健秩聚合来识别关键调节基因,如 PPARG、CEBPA 和 EP300。网络分析进一步强调了、、和作为脂肪生成及其成熟状态的潜在关键因子,通过 RT-PCR 进行了验证。虽然关键的脂肪生成因子表现出平台化的表达水平,表明早期分化事件,但这项研究强调了胚胎干细胞在模拟脂肪生成中的价值。这些发现有助于我们理解脂肪细胞分化,并对针对代谢疾病的治疗策略具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d30c/11395306/516a5f51173a/ijms-25-09154-g001.jpg

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