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

Mengxia Fu; Lian Xu; Xiaohui Chen; Weiqing Han; Chengchao Ruan; Jun Li; Chenleng Cai; Maoqing Ye; Pingjin Gao

doi:10.1161/ATVBAHA.119.312838

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

Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1629-1644. doi: 10.1161/ATVBAHA.119.312838. Epub 2019 Jun 13.

Authors

Mengxia Fu¹, Lian Xu¹, Xiaohui Chen¹, Weiqing Han¹, Chengchao Ruan¹, Jun Li², Chenleng Cai³, Maoqing Ye¹, Pingjin Gao¹

Affiliations

¹ From the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension (M.F., L.X., X.C., W.H., C.R., M.Y., P.G.), Shanghai Jiao Tong University School of Medicine, China.
² Department of Cardiology, Shanghai General Hospital (J.L.), Shanghai Jiao Tong University School of Medicine, China.
³ Riley Heart Research Center, and Herman Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (C.C.).

PMID: 31189430
DOI: 10.1161/ATVBAHA.119.312838

Abstract

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⁺;PPARγ^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 PAAT.

Conclusions: PAAT has distinctive anatomic features and developmental processes. Most PAAT adipocytes are originated from NCCs which derive from ectoderm. NCCs are progenitors not only of white adipocytes but also of brown adipocytes. This study indicates that the PAAT is derived from multiple cell lineages, the adipocytes derived from different origins have distinct transcriptional profiles, and PAAT plays a critical role in Ang II-induced common carotid artery inflammation and remodeling.Visual OvervieW: An online visual overview is available for this article.

Keywords: adipose tissue; angiotensin II; brown; mice; neural crest; stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Brown / cytology*
Adipogenesis*
Adipose Tissue / cytology
Adipose Tissue / physiology*
Angiotensin II / pharmacology
Animals
Aorta, Thoracic / cytology
Carotid Artery, Common / cytology
Cell Differentiation
Cell Lineage
Cells, Cultured
Gene Expression Profiling
Male
Mice
Mice, Inbred C57BL
Neural Crest / cytology*
PPAR gamma / physiology
Wnt1 Protein / physiology

Substances

PPAR gamma
Wnt1 Protein
Wnt1 protein, mouse
Angiotensin II