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Transcriptome profiling of differentiating adipose-derived stem cells across species reveals new genes regulating adipogenesis
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 4.8 ) Pub Date : 2023-08-10 , DOI: 10.1016/j.bbalip.2023.159378
Jiangang Han 1 , Xiaojie Li 2 , Benmeng Liang 2 , Sijia Ma 3 , Yabin Pu 2 , Fuqing Yu 4 , Jian Lu 4 , Yuehui Ma 2 , David E MacHugh 5 , Lin Jiang 2
Affiliation  

Adipose-derived stem cells (ADSCs) that are enriched in adipose tissue with multilineage differentiation potential have become an important tool in therapeutic research and tissue engineering. Certain breeds of sheep exhibit a unique fat tail trait such that tail tissue accounts for approximately 10 % of body weight and can provide an excellent source of ADSCs. Here, we describe isolation of primary ADSCs from ovine embryonic fat tail tissues that displayed high self-renewal capacity, multilineage differentiation and excellent adipogenic ability. Through transcriptome analysis covering ADSCs differentiating into adipocytes, 37 transcription factors were involved in early transcriptional events that initiate a regulatory cascade of adipogenesis; the entire adipogenic activity consists of a reduction in proliferation ability and upregulation of genes related to lipid generation and energy metabolism, as well as several genes associated with myogenesis. Furthermore, Comparative transcriptome analysis across species (sheep, human, and mouse) revealed enhanced basal metabolic ability in differentiating ovine ADSCs, which may relate to the excellent adipogenic capability of these cells. We also identified a small evolutionarily conserved gene set, consisting of 21 and 22 genes exhibiting increased and decreased expression, respectively. Almost half (20) of these genes have not previously been reported to regulate adipogenesis in mammals. In this study, we identified important regulators that trigger ovine adipocyte differentiation, main biological pathways involved in adipogenesis as well as the evolutionarily conserved genes governing adipogenic process across species. Our study provides a novel excellent biomaterial and novel genes regulating adipogenesis for cellular transplantation therapy and investigations of fat metabolism.



中文翻译:

跨物种分化脂肪干细胞的转录组分析揭示了调节脂肪生成的新基因

脂肪组织中富集的脂肪干细胞(ADSC)具有多向分化潜能,已成为治疗研究和组织工程的重要工具。某些品种的绵羊表现出独特的肥尾性状,尾部组织约占体重的10%,可以提供ADSC的极好来源。在这里,我们描述了从绵羊胚胎脂肪尾组织中分离出的原代脂肪干细胞,其表现出高自我更新能力、多谱系分化和优异的成脂能力。通过对 ADSC 分化为脂肪细胞的转录组分析,发现 37 个转录因子参与了启动脂肪生成调控级联的早期转录事件;整个脂肪生成活性包括增殖能力的降低和与脂质生成和能量代谢相关的基因以及与肌生成相关的几个基因的上调。此外,跨物种(绵羊、人类和小鼠)的比较转录组分析揭示了绵羊 ADSC 分化的基础代谢能力增强,这可能与这些细胞优异的成脂能力有关。我们还鉴定了一个小的进化保守基因集,由 21 个和 22 个分别表现出表达增加和减少的基因组成。这些基因中近一半 (20) 以前从未被报道过调节哺乳动物的脂肪形成。在这项研究中,我们确定了触发绵羊脂肪细胞分化的重要调节因子、参与脂肪形成的主要生物途径以及控制跨物种脂肪形成过程的进化保守基因。我们的研究为细胞移植治疗和脂肪代谢研究提供了一种新型的优良生物材料和调控脂肪生成的新型基因。

更新日期:2023-08-10
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