Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development.
Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development.
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DOI：
10.1016/j.celrep.2023.112166
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发表时间：
2023-03-28
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
不同的白色脂肪储存库的不同位置表明解剖特异性发育调节，一个相对研究不足的概念。在这里，我们报告了一个人口的Tcf 21谱系细胞（Tcf 21 LCs）目前只在内脏脂肪组织（VAT），动态有助于VAT的发展和扩大。在发育过程中，Tcf 21谱系产生脂肪细胞。在成年小鼠中，Tcf 21 LC转化为纤维化或静止状态。多组学分析显示Tcf 21 LC中一致的基因表达和染色质可及性变化，在此基础上，我们构建了一个基因调控网络Tcf 21 LC活动。此外，单细胞RNA测序（scRNA-seq）鉴定了Tcf 21 LC的异质性。Tcf 21的缺失促进Tcf 21 LC的脂肪形成和发育进展，从而在饮食诱导的肥胖症的背景下改善代谢健康。机制研究表明，Tcf 21对脂肪形成的抑制作用至少部分是通过Dlk 1表达加重介导的。Liu等报道了Tcf 21，一种VAT特异性基因，是MPC所独有的。Tcf 21 LC直接促进VAT的发展，但由于转录和染色质可及性的变化，在成年人中具有有限的脂肪形成。Tcf 21的缺失通过减少Dlk 1表达促进内脏脂肪形成，改善肥胖小鼠的代谢健康。
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. Liu et al. report that Tcf21, a VAT-specific gene, is exclusive to MPCs. Tcf21 LCs directly contribute to VAT development but have limited adipogenesis in adults because of transcriptional and chromatin accessibility changes. Loss of Tcf21 promotes visceral adipogenesis by reducing Dlk1 expression, improving the metabolic health of obese mice.
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