Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development

Qianglin Liu; Chaoyang Li; Buhao Deng; Peidong Gao; Leshan Wang; Yuxia Li; Mohammad Shiri; Fozi Alkaifi; Junxing Zhao; Jacqueline M. Stephens; Constantine A. Simintiras; Joseph Francis; Jiangwen Sun; Xing Fu

Cell Reports (Mar 2023)

Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development

Qianglin Liu,
Chaoyang Li,
Buhao Deng,
Peidong Gao,
Leshan Wang,
Yuxia Li,
Mohammad Shiri,
Fozi Alkaifi,
Junxing Zhao,
Jacqueline M. Stephens,
Constantine A. Simintiras,
Joseph Francis,
Jiangwen Sun,
Xing Fu

Affiliations

Qianglin Liu: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA
Chaoyang Li: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA
Buhao Deng: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA; Department of Animal Sciences, Shanxi Agricultural University, Taigu, Shanxi, China
Peidong Gao: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA
Leshan Wang: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA
Yuxia Li: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA
Mohammad Shiri: Department of Computer Science, Old Dominion University, Norfolk, VA, USA
Fozi Alkaifi: Department of Computer Science, Old Dominion University, Norfolk, VA, USA
Junxing Zhao: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA; Department of Animal Sciences, Shanxi Agricultural University, Taigu, Shanxi, China
Jacqueline M. Stephens: Pennington Biomedical Research Center, Baton Rouge, LA, USA; Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA
Constantine A. Simintiras: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA
Joseph Francis: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
Jiangwen Sun: Department of Computer Science, Old Dominion University, Norfolk, VA, USA; Corresponding author
Xing Fu: School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112166

Abstract

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Summary: Distinct locations of different white adipose depots suggest anatomy-specific developmental regulation, a relatively understudied concept. Here, we report a population of Tcf21 lineage cells (Tcf21 LCs) present exclusively in visceral adipose tissue (VAT) that dynamically contributes to VAT development and expansion. During development, the Tcf21 lineage gives rise to adipocytes. In adult mice, Tcf21 LCs transform into a fibrotic or quiescent state. Multiomics analyses show consistent gene expression and chromatin accessibility changes in Tcf21 LC, based on which we constructed a gene-regulatory network governing Tcf21 LC activities. Furthermore, single-cell RNA sequencing (scRNA-seq) identifies the heterogeneity of Tcf21 LCs. Loss of Tcf21 promotes the adipogenesis and developmental progress of Tcf21 LCs, leading to improved metabolic health in the context of diet-induced obesity. Mechanistic studies show that the inhibitory effect of Tcf21 on adipogenesis is at least partially mediated via Dlk1 expression accentuation.

CP: Metabolism

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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