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PDGFRα/PDGFRβ负调控脂肪形成
作者:小柯机器人 发布时间:2020/3/31 13:27:54

美国俄克拉荷马州医学研究基金会心血管生物学研究项目Lorin E. Olson研究组取得一项新突破。他们利用镶嵌突变分析确定血小板来源的生长因子受体PDGFRα/PDGFRβ是脂肪形成的负调节因子。该项研究成果发表在2020330日出版的《细胞-干细胞》杂志上。

他们将血统追踪和功能分析相结合,采用顺序双重重组酶方法,该方法通过Cre / lox重组与相关的Flp / frt报告基因来追踪单个细胞的命运,从而创建了镶嵌Pdgfr突变细胞。

使用镶嵌谱系标记,他们显示,在产后生长和成年期,脂肪细胞是从Pdgfra谱系来源的。相反,在产后生长期间,脂肪细胞仅源自镶嵌Pdgfrb谱系。从功能上讲,PDGFRα的产后镶嵌缺失促进脂肪生成,而成人缺失则促进β3-肾上腺素受体诱导的米色脂肪细胞的形成。PDGFRβ的镶嵌缺失还促进了白色、棕色和米色的脂肪形成。

这些数据表明,两种PDGFR都是脂肪细胞分化的细胞自主抑制因子,并暗示PDGF信号的下调是从脂肪细胞祖细胞(APs)过渡到脂肪细胞的关键事件。

据介绍,AP表达PDGFRsPDGFRαPDGFRβPDGFRα信号转导升高会抑制脂肪生成并促进纤维化。但是,PDGFRAP中的功能仍不清楚。

附:英文原文

Title: Mosaic Mutant Analysis Identifies PDGFRα/PDGFRβ as Negative Regulators of Adipogenesis

Author: Chengyi Sun, Hiromi Sakashita, Jang Kim, Zifeng Tang, G. Michael Upchurch, Longbiao Yao, William L. Berry, Timothy M. Griffin, Lorin E. Olson

Issue&Volume: 2020-03-30

Abstract: Adipocyte progenitors (APs) express platelet-derived growth factor receptors (PDGFRs),PDGFRα and PDGFRβ. Elevated PDGFRα signaling inhibits adipogenesis and promotes fibrosis;however, the function of PDGFRs in APs remains unclear. We combined lineage tracingand functional analyses in a sequential dual-recombinase approach that creates mosaicPdgfr mutant cells by Cre/lox recombination with a linked Flp/frt reporter to track individualcell fates. Using mosaic lineage labeling, we show that adipocytes are derived fromthe Pdgfra lineage during postnatal growth and adulthood. In contrast, adipocytes are only derivedfrom the mosaic Pdgfrb lineage during postnatal growth. Functionally, postnatal mosaic deletion of PDGFRαenhances adipogenesis and adult deletion enhances β3-adrenergic-receptor-induced beigeadipocyte formation. Mosaic deletion of PDGFRβ also enhances white, brown, and beigeadipogenesis. These data show that both PDGFRs are cell-autonomous inhibitors of adipocytedifferentiation and implicate downregulation of PDGF signaling as a critical eventin the transition from AP to adipocyte.

DOI: 10.1016/j.stem.2020.03.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30096-5

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
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