Doctor of Philosophy (PhD)
School of Animal Science
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) that are present exclusively in visceral adipose tissue (VAT) and dynamically contribute to VAT development and expansion. In vivo data demonstrated that during development, Tcf21 LCs will give rise to adipocytes. In young mice, Tcf21 LCs will proliferate into a large progenitor cell niche and then differentiate into adipocytes between 2 to 3 weeks of age. In adult mice, Tcf21 LCs transform into a fibrotic or quiescent state and lose their adipogenic potential. Multiomic analyses show gene expression and chromatin accessibility changes in Tcf21 LCs. Gene set enrichment analysis (GSEA) revealed biological processes (BPs) enriched in mice under different conditions where “Fat cell differentiation” was enriched in younger or short term high-fat diet fed mice. The ATAC results shows that the gene expression of Tcf21 LCs has a strong correlation with promotor accessibility and enhancer accessibility. Based on these data, we constructed a gene regulatory network that represents Tcf21 LC activities and found that Tcf21 may be an adipogenesis inhibitor. Furthermore, single-cell RNA-seq identifies the heterogeneity of Tcf21 LCs. Tcf21 LCs can be mainly divided into Dpp4+ and Icam+ subpopulations and dynamic contributions of different Tcf21 LC subpopulations to VAT development and pathological expansion. Loss of Tcf21 in VAT will promote adipogenesis and developmental progress of Tcf21 LCs, leading to improved metabolic health in the context of diet-induced obesity. Analysis of Tcf21 direct target gene identified that Dlk1 is a downstream adipogenesis inhibitor in Tcf21 LCs. Lose-of and gain-of function of Dlk1 verified that the inhibitory effect of Tcf21 on adipogenesis is at least partially mediated via Dlk1 expression.
Liu, Qianglin, "Tcf21 and visceral adipogenic progenitors" (2023). LSU Doctoral Dissertations. 6197.
Available for download on Friday, June 28, 2030