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A Wnt/β-catenin signaling driven adipocyte population required for beiging and glucose homeostasis

The scripts in this repository contains all of the code for scRNA-seq and scATAC-seq analyses (10x Genomics) that was run to create the figures in the manuscript.

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Zhi Liu1,2,4, Tian Chen1,2,4, Sicheng Zhang1,2, Tianfang Yang1, Yun Gong3, Hong-Wen Deng3, Ding Bai2, Weidong Tian2*, and YiPing Chen1,*

  1. Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, USA
  2. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
  3. Tulane Center of Biomedical Informatics and Genomic, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA, USA
  4. These authors contributed equally

*Correspondence: drtwd@sina.com (W.T.), ychen@tulane.edu (Y.C.)

Abstract

Wnt/β-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of Wnt/β-catenin signaling driven adipocytes in embryonic and adult mouse fat depots. We showed that Wnt/β-catenin signaling activation in these cells relies on AKT/mTOR signaling intracellularly and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Using genetic lineage-tracing and targeted cell ablation mouse models, these adipocytes were shown to not only convert into beige adipocytes directly but be also required for beige fat recruitment under thermal challenge, demonstrating a central role in initiating adaptive thermogenesis. Mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging and systemic glucose homeostasis.

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Scripts for scRNA-seq and scATAC-seq

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