Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion
Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion
复制标题
DOI：
10.1242/dev.125336
复制
发表时间：
2015-08-01
期刊：
影响因子：
4.6
通讯作者：
Koh, Gou Young
中科院分区：
文献类型：
--
作者：
Hong, Ki Yong;Bae, Hosung;Koh, Gou Young
尽管脂肪组织作为代谢性疾病的治疗靶点越来越受到关注，但对脂肪细胞前体细胞（前脂肪细胞）的身份和胚胎发育期间脂肪组织的形成仍然知之甚少。本研究通过直接观察、谱系追踪和培养系统，阐明了小鼠白色脂肪组织中前脂肪细胞在胚胎发生过程中的身份和动态过程。令人惊讶的是，我们发现缺乏脂质但周脂蛋白（+）或脂联素（+）增殖的前脂肪细胞在胚胎第16.5天开始出现，并且这些细胞经历活跃的增殖直到出生。此外，这些前脂肪细胞居住的集群和分布沿着生长的脂肪血管。重要的是，胚胎前脂肪细胞表现出相当多的干细胞标志物，如CD24，CD29和PDGFR α的共表达，一小部分前脂肪细胞来源于PDGFR β（+）壁细胞，与基质血管部分中存在的成人前脂肪细胞相反。进一步的分析与体外和离体培养系统揭示了一个逐步的，但动态调节前脂肪细胞的形成和分化在产前脂肪形成。综上所述，我们揭示了胚胎前脂肪细胞的身份和特征，这对胚胎发育过程中脂肪组织的形成和扩张至关重要。
Despite the growing interest in adipose tissue as a therapeutic target of metabolic diseases, the identity of adipocyte precursor cells (preadipocytes) and the formation of adipose tissue during embryonic development are still poorly understood. Here, we clarified the identity and dynamic processes of preadipocytes in mouse white adipose tissue during embryogenesis through direct examination, lineage tracing and culture systems. Surprisingly, we found that lipid-lacking but perilipin(+) or adiponectin(+) proliferating preadipocytes started to emerge at embryonic day 16.5, and these cells underwent active proliferation until birth. Moreover, these preadipocytes resided as clusters and were distributed along growing adipose vasculatures. Importantly, the embryonic preadipocytes exhibited considerable coexpression of stem cell markers, such as CD24, CD29 and PDGFR alpha, and a small portion of preadipocytes were derived from PDGFR beta(+) mural cells, in contrast to the adult preadipocytes present in the stromal vascular fraction. Further analyses with in vitro and ex vivo culture systems revealed a stepwise but dynamic regulation of preadipocyte formation and differentiation during prenatal adipogenesis. To conclude, we unraveled the identity and characteristics of embryonic preadipocytes, which are crucial for the formation and expansion of adipose tissue during embryogenesis.