Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion.

Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion.
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DOI:
10.1016/j.celrep.2014.06.060
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发表时间:
2014-08-07
期刊:
影响因子:
8.8
通讯作者:
Sul HS
Sul HS
中科院分区:
生物学1区
文献类型:
--
作者:
Hudak CS;Gulyaeva O;Wang Y;Park SM;Lee L;Kang C;Sul HS

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Pref-1是一种含有EGF重复序列的蛋白质,可抑制脂肪细胞分化。为了更好地理解白色脂肪组织(WAT)的起源和发育,我们使用Pref-1启动子产生用于瞬时或永久荧光标记细胞的转基因小鼠模型,促进诱导消融。我们发现,Pref-1标记的细胞保持增殖能力,是非常早期的脂肪前体,在Zfp 423或PPARg表达之前。此外,Pref-1标记的细胞建立脂肪前体作为间充质,而不是内皮或周细胞来源。在胚胎发生过程中,Pref-1标记的细胞最早出现在背侧肠系膜区域早在E10.5。这些细胞在E17.5时在皮下区域变成富含脂质的脂肪细胞,而内脏WAT在出生后发展。最后,去除Pref-1标记的细胞不仅防止胚胎WAT发育,而且防止高脂肪喂养后的成年脂肪扩增,证明了脂肪形成需要Pref-1细胞。
Pref-1 is an EGF-repeat containing protein that inhibits adipocyte differentiation. To better understand the origin and development of white adipose tissue (WAT), we generated transgenic mouse models for transient or permanent fluorescent labeling of cells using the Pref-1 promoter, facilitating inducible ablation. We show that Pref-1 marked cells retain proliferative capacity and are very early adipose precursors, prior to expression of Zfp423 or PPAR g. In addition, Pref-1 marked cells establish adipose precursors as mesenchymal, but not endothelial or pericyte in origin. During embryogenesis, Pref-1 marked cells first appear in the dorsal mesenteric region as early as E10.5. These cells become lipid-laden adipocytes at E17.5 in the subcutaneous region, whereas visceral WAT develops after birth. Finally, ablation of Pref-1 marked cells prevents not only embryonic WAT development but also later adult adipose expansion upon high fat feeding, demonstrating the requirement of Pref-1 cells for adipogenesis.
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