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
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.
