Neural Crest Cells Differentiate Into Brown Adipocytes and Contribute to Periaortic Arch Adipose Tissue Formation

作者：Mengxia Fu, Lian Xu, Xiaohui Chen, Weiqing Han, Cheng‐Chao Ruan, Jun Li, Chen‐Leng Cai, Maoqing Ye, Pingjin Gao · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2019 · DOI：10.1161/atvbaha.119.312838 · 被引用次数：42 · 研究领域：Congenital heart defects research、Cardiovascular Disease and Adiposity、Peroxisome Proliferator-Activated Receptors

Objective: Periaortic arch adipose tissue (PAAT) plays critical roles in regulating vascular homeostasis; however, its anatomic features, developmental processes, and origins remain unclear. Approach and Results: Anatomic analysis and genetic lineage tracing of Wnt1 (wingless-type MMTV [mouse mammary tumor virus] integration site family member 1)-Cre + ;Rosa26 RFP/+ mice, Myf5 (myogenic factor 5)-Cre + ;Rosa26 RFP/+ mice, and SM22α-Cre + ;Rosa26 RFP/+ mice are performed, and the results show that PAAT has unique anatomic features, and the developmental processes of PAAT are independent of the others periaortic adipose tissues. PAAT adipocytes are mainly derived from neural crest cells (NCCs) rather than from Myf5 + progenitors. Most PAAT adipocyte progenitors expressed SM22α + (smooth muscle protein 22-alpha) during development. Using Wnt1-Cre + ; PPAR γ flox/flox mice, we found that knockout of PPAR (peroxisome proliferator-activated receptor)-γ in NCCs results in PAAT developmental delay and dysplasia, further confirming that NCCs contribute to PAAT formation. And we further indicated PAAT dysplasia aggravates Ang II (angiotensin II)–induced inflammation and remodeling of the common carotid artery close to aorta arch. We also found that NCCs can be differentiated into both brown and white adipocytes in vivo and in vitro. RNA sequencing results suggested NCC-derived adipose tissue displays a distinct transcriptional profile compared with the non-NCC-derived adipose tissue in...