Kang Jengmin, Kanugovi Abhijnya, Stella M Pilar J, Frimand Zofija, Farup Jean, Urtasun Andoni, Liu Shixuan, Clausen Anne-Sofie, Ishak Heather, Bui Summer, Kim Soochi, Ezran Camille, Botvinnik Olga, Porpiglia Ermelinda, Krasnow Mark A, de Morree Antoine, Rando Thomas A
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
Nat Commun. 2025 Jun 24;16(1):5370. doi: 10.1038/s41467-025-58897-x.
The development of non-human primate models is essential for the fields of developmental and regenerative biology because those models will more closely approximate human biology than do murine models. Based on single cell RNAseq and fluorescence-activated cell sorting, we report the identification and functional characterization of two quiescent stem cell populations (skeletal muscle stem cells (MuSCs) and mesenchymal stem cells termed fibro-adipogenic progenitors (FAPs)) in the non-human primate Microcebus murinus (the gray mouse lemur). We demonstrate in vivo proliferation, differentiation, and self-renewal of both MuSCs and FAPs. By combining cell phenotyping with cross-species molecular profiling and pharmacological interventions, we show that mouse lemur MuSCs and FAPs are more similar to human than to mouse counterparts. We identify unexpected gene targets involved in regulating primate MuSC proliferation and primate FAP adipogenic differentiation. Moreover, we find that the cellular composition of mouse lemur muscle better models human muscle than does macaque (Macaca fascicularis) muscle. Finally, we note that our approach presents as a generalizable pipeline for the identification, isolation, and characterization of stem cell populations in new animal models.
非人灵长类动物模型的发展对于发育生物学和再生生物学领域至关重要，因为这些模型比小鼠模型更接近人类生物学。基于单细胞RNA测序和荧光激活细胞分选技术，我们报告了在非人类灵长类动物小鼠狐猴（灰鼠狐猴）中鉴定出两种静止干细胞群（骨骼肌干细胞（MuSCs）和被称为纤维脂肪生成祖细胞（FAPs）的间充质干细胞）并对其进行功能表征。我们展示了MuSCs和FAPs在体内的增殖、分化和自我更新能力。通过将细胞表型分析与跨物种分子谱分析和药物干预相结合，我们发现小鼠狐猴的MuSCs和FAPs与人类的对应细胞比与小鼠的更相似。我们鉴定出了参与调节灵长类动物MuSC增殖和灵长类动物FAP脂肪生成分化的意外基因靶点。此外，我们发现小鼠狐猴肌肉的细胞组成比猕猴（食蟹猴）肌肉更能模拟人类肌肉。最后，我们指出我们的方法是一种可推广的流程，用于在新的动物模型中鉴定、分离和表征干细胞群。
