State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases &, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, People's Republic of China.
Stem Cell Rev Rep. 2023 Aug;19(6):1937-1953. doi: 10.1007/s12015-023-10563-9. Epub 2023 May 24.
Obesity is a common chronic health problem that requires lifelong efforts for the successful treatment. The proliferation of ADSCs is an essential step in the development of obesity. Identifying key regulators of ADSCs will be a novel strategy for adipogenesis inhibition and obesity prevention. In this study, transcriptomes of 15532 ADSCs were firstly profiled by single cell RNA-sequencing. On the basis of gene expression patterns, 15 cell subpopulations (six defined cell types) were distinguished. A subpopulation was identified as CD168 ADSCs, and it was demonstrated to play a vital role in ADSCs proliferation. Furthermore, Hmmr, a specific marker gene of CD168 ADSCs was found to be a critical gene associated with ADSCs proliferation and mitosis. Hmmr knockout resulted that ADSCs growth nearly arrested and aberrant nuclear division occurred. Finally, it was revealed that Hmmr promoted ADSCs proliferation through the extracellular signal-regulated kinase 1/2 signaling pathway. This study identified Hmmr as a key regulator in ADSCs proliferation and mitosis, and suggested that Hmmr may be a novel target for obesity prevention.
肥胖是一种常见的慢性健康问题，需要终生努力才能成功治疗。脂肪干细胞的增殖是肥胖发生的一个重要步骤。鉴定脂肪干细胞的关键调节因子将是抑制脂肪生成和预防肥胖的新策略。在这项研究中，我们首先通过单细胞 RNA 测序对 15532 个 ADSCs 的转录组进行了分析。基于基因表达模式，我们区分了 15 个细胞亚群（六种定义的细胞类型）。一个亚群被鉴定为 CD168 ADSCs，它被证明在 ADSCs 增殖中起着至关重要的作用。此外，我们发现 Hmmr 是 CD168 ADSCs 的特异性标记基因，与 ADSCs 的增殖和有丝分裂密切相关。Hmmr 敲除导致 ADSCs 生长几乎停滞，出现异常核分裂。最后，我们揭示了 Hmmr 通过细胞外信号调节激酶 1/2 信号通路促进 ADSCs 的增殖。这项研究确定了 Hmmr 是 ADSCs 增殖和有丝分裂的关键调节因子，并表明 Hmmr 可能是预防肥胖的一个新靶点。
