Rivera-Gonzalez Guillermo C, Butka Emily G, Gonzalez Carolynn E, Mintz Rachel L, Kleb Sarah S, Josephson Violet, Kong Wenjun, Jindal Kunal, Kamimoto Kenji, Shook Brett A, Rodeheffer Matthew S, Morris Samantha A
Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Cell Stem Cell. 2025 Aug 7;32(8):1267-1284.e8. doi: 10.1016/j.stem.2025.07.004. Epub 2025 Jul 30.
White adipose tissue supports essential physiological functions through adipocyte precursor cells (APCs), comprising progenitors and preadipocytes, which generate mature adipocytes during depot expansion. Using single-cell RNA sequencing-based lineage tracing, we characterize APCs in skin adipose tissue-a depot uniquely capable of rapid adipogenesis compared with other sites, such as inguinal adipose. We identify a previously uncharacterized population of immature preadipocytes and reveal distinct differentiation potentials among APCs. Contrary to traditional stepwise differentiation models, progenitors predominantly generate committed preadipocytes, whereas preexisting preadipocytes accumulate in immature states with divergent potential. Leveraging this refined APC hierarchy, we uncover Sox9 as a crucial regulator of progenitor proliferation and adipogenic differentiation. Cross-depot transplantation further demonstrates how intrinsic and extrinsic factors differentially regulate skin progenitor behavior, highlighting distinct adipogenic dynamics between skin and inguinal depots. Together, these insights redefine the cellular hierarchy and molecular mechanisms underpinning rapid adipogenesis in skin adipose tissue.
白色脂肪组织通过脂肪细胞前体细胞(APC)支持重要的生理功能,APC包括祖细胞和前脂肪细胞,在脂肪库扩张期间产生成熟脂肪细胞。利用基于单细胞RNA测序的谱系追踪技术,我们对皮肤脂肪组织中的APC进行了表征,与腹股沟脂肪等其他部位相比,皮肤脂肪库具有独特的快速脂肪生成能力。我们鉴定出一种以前未被表征的未成熟前脂肪细胞群体,并揭示了APC之间不同的分化潜能。与传统的逐步分化模型相反,祖细胞主要产生定向前脂肪细胞,而现有的前脂肪细胞以具有不同潜能的未成熟状态积累。利用这种精细的APC层级结构,我们发现Sox9是祖细胞增殖和成脂分化的关键调节因子。跨脂肪库移植进一步证明了内在和外在因素如何差异调节皮肤祖细胞行为,突出了皮肤和腹股沟脂肪库之间不同的脂肪生成动态。总之,这些见解重新定义了皮肤脂肪组织中快速脂肪生成的细胞层级结构和分子机制。