Single-cell multiomics reveals multiple adipogenic pathways and diverse multilineage specializations during embryonic fat tail morphogenesis

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-03 DOI:10.1016/j.isci.2025.113496

Jiangang Han , Sijia Ma , Qiuxia Wei , Zhengwei Zhao , Yuhetian Zhao , Yabin Pu , Qianjun Zhao , Xiaohong He , Yuehui Ma , David E. MacHugh , Lin Jiang

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Abstract

Embryonic adipogenesis remains one of the least understood aspects of adipose biology in mammals due to time sensitivity, limited tissue volume, and ethical concerns. Here, we uniquely applied single-cell multi-omics sequencing to the developing adipose tissues of fat-tailed sheep, characterized by genetically determined, significant fat deposition in the tail during embryogenesis. Our dataset spans all stages of adipogenesis (E50 to E80), revealing three major cellular origins of fat deposition: progenitor and stem cells, connective tissue progenitors, and vascular smooth muscle cells. By integrating scRNA-seq, snATAC-seq, and functional validation, we identified key enhancer-driven gene regulatory networks (eGRNs) governing adipogenesis, with DBI emerging as a critical regulator through its interaction with PPARG. Additionally, we delineated developmental trajectories and unique eGRNs underlying angiogenesis, osteogenesis, chondrogenesis, and myogenesis associated with fat formation. Our findings provide novel insights into embryonic adipogenesis in mammals and reveal critical regulons governing lineage specialization.

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单细胞多组学揭示了胚胎脂肪尾形态发生过程中的多种脂肪形成途径和多种多谱系特化

由于时间敏感性、有限的组织体积和伦理问题，胚胎脂肪形成仍然是哺乳动物脂肪生物学中最不为人所知的方面之一。在这里，我们独特地将单细胞多组学测序应用于胖尾羊的发育脂肪组织，其特征是遗传决定的，在胚胎发生期间尾巴有显著的脂肪沉积。我们的数据集涵盖了脂肪形成的所有阶段（E50至E80），揭示了脂肪沉积的三个主要细胞来源：祖细胞和干细胞、结缔组织祖细胞和血管平滑肌细胞。通过整合scRNA-seq、snATAC-seq和功能验证，我们确定了控制脂肪形成的关键增强子驱动基因调控网络（egrn）， DBI通过与PPARG的相互作用成为关键的调控因子。此外，我们描述了与脂肪形成相关的血管生成、骨生成、软骨生成和肌肉生成的发育轨迹和独特的egrn。我们的发现为哺乳动物胚胎脂肪形成提供了新的见解，并揭示了支配谱系特化的关键规律。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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