Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity.
Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity.
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DOI：
10.1371/journal.pone.0017834
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发表时间：
2011-03-31
期刊：
影响因子：
3.7
通讯作者：
Azziz R
中科院分区：
文献类型：
--
作者：
Chazenbalk G;Bertolotto C;Heneidi S;Jumabay M;Trivax B;Aronowitz J;Yoshimura K;Simmons CF;Dumesic DA;Azziz R
先前的研究强调了脂肪组织巨噬细胞（ATM）、脂肪干细胞（ASC）和脂肪细胞的谱系和表型之间的复杂关系，表明这些细胞具有高度的可塑性。在本研究中，使用一种新的共培养系统，我们进一步表征了ATM，ASCs和脂肪细胞之间的相互作用。从人脂肪组织中分离人脂肪细胞和含有ATM和ASC的基质血管部分，并共培养24小时。在共培养之前和之后使用FACS来表征ATM和ASC。通过DLK（前脂肪细胞）、CD 14和CD 68（ATM）、CD 34（ASC）的免疫染色和脂质滴的尼罗红染色表征共培养后产生的前脂肪细胞。qRT-PCR用于定量脂肪形成标志物，如C/EBPα和PPARγ。在共培养之前使用新的荧光纳米珠谱系追踪方法，其中荧光纳米珠被CD 68（+）ATM内化。脂肪细胞与ATM和ASC共培养增加了新的前脂肪细胞的形成，从而增加了脂质积累和C/EBPα和PPARγ基因表达。共培养后产生的前脂肪细胞对前脂肪细胞、ATM和ASC的标志物呈阳性。此外，荧光纳米珠在共培养前被ATM内化，并且共培养后形成的新的前脂肪细胞也含有荧光纳米珠，这表明新的前脂肪细胞部分起源于ATM。CD 34（+）/CD 68（+）/DLK（+）细胞球的形成支持了ATM、ASCs和前脂肪细胞的相互作用。脂肪细胞、ATM和ASC之间的相互作用促进前脂肪细胞的形成。这种新的脂肪形成途径的调节涉及ATM向前脂肪细胞的分化。CD 34（+）/CD 68（+）/DLK（+）细胞聚集在球体中的存在表明这些细胞类型之间的旁分泌相互作用在新的前脂肪细胞的产生和增殖中起重要作用。这种现象可能反映了脂肪组织的体内可塑性，其中ATM在炎症和其他疾病状态期间发挥额外的作用。了解这种新的途径可能会影响脂肪形成，从而导致肥胖，炎症和2型糖尿病的新疗法。
Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes. Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes), CD14 and CD68 (ATMs), CD34 (ASCs), and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPα and PPARγ. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+) ATMs. Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPα and PPARγ gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+)/CD68(+)/DLK (+) cell spheres supported the interaction of ATMs, ASCs and preadipocytes. Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+)/CD68(+)/DLK(+) cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and proliferation of new preadipocytes. This phenomenon may reflect the in vivo plasticity of adipose tissue in which ATMs play an additional role during inflammation and other disease states. Understanding this novel pathway could influence adipogenesis, leading to new treatments for obesity, inflammation, and type 2 diabetes.
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影响因子：
5.2
作者：
Kuwana, Masataka;Okazaki, Yuka;Ikeda, Yasuo
通讯作者：
Ikeda, Yasuo
影响因子：
3.6
作者：
Moseley, Timothy A.;Zhu, Min;Hedrick, Marc H.
通讯作者：
Hedrick, Marc H.
影响因子：
4.8
作者：
Lacasa, Daniele;Taleb, Soraya;Clement, Karine
通讯作者：
Clement, Karine
影响因子：
7.7
作者：
Nishimura, Satoshi;Manabe, Ichiro;Sugiura, Seiryo
通讯作者：
Sugiura, Seiryo
DOI：
10.1073/pnas.0911647107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Kuroda, Yasumasa;Kitada, Masaaki;Dezawa, Mari
通讯作者：
Dezawa, Mari