Defining the lineage of thermogenic perivascular adipose tissue.

Defining the lineage of thermogenic perivascular adipose tissue.
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DOI:
10.1038/s42255-021-00380-0
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发表时间:
2021-04
期刊:
影响因子:
20.8
通讯作者:
Seale P
Seale P
中科院分区:
医学1区
文献类型:
--
作者:
Angueira AR;Sakers AP;Holman CD;Cheng L;Arbocco MN;Shamsi F;Lynes MD;Shrestha R;Okada C;Batmanov K;Susztak K;Tseng YH;Liaw L;Seale P

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棕色脂肪组织可以消耗大量的能量,因此增加其大小或活性是对抗代谢性疾病的一种有前途的治疗方法。在人类中,棕色脂肪细胞的主要沉积与大血管密切相关,对应于血管周围脂肪组织(PVAT)。然而,PVAT的细胞起源还知之甚少。在这里,我们确定了小鼠和人类血管周围脂肪细胞前体细胞的身份。在小鼠中,胸腔PVAT由成纤维细胞系发展而来,由前体细胞(PDGFRA+;Ly6a+;PPARG-)和前体脂肪细胞(PDGFRA+;Ly6a+;PPARG+)组成,它们在转录上与白色脂肪组织中的类似细胞类型相似。有趣的是,成年动物的主动脉外膜含有一群成脂的平滑肌细胞(MYH11+;PDGFRA-;PPARG+),它们有助于血管周围脂肪细胞的形成。同样,单核RNAseq显示,人的PVAT含有推测的成纤维细胞和SMC样脂肪细胞前体细胞。综上所述,这些研究确定了发热性PVAT的不同祖细胞群体,为开发增强棕色脂肪活性的策略提供了基础。
Brown adipose tissue can expend large amounts of energy, and therefore increasing its size or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. Here, we determine the identity of perivascular adipocyte progenitors in mice and humans. In mice, thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra+; Ly6a+; Pparg-) and preadipocytes (Pdgfra+; Ly6a+; Pparg+), which share transcriptional similarity with analogous cell types in white adipose tissue. Interestingly, the aortic adventitia of adult animals contains a population of adipogenic smooth muscle cells (SMCs) (Myh11+; Pdgfra-; Pparg+) that contribute to perivascular adipocyte formation. Similarly, human PVAT contains presumptive fibroblastic and SMC-like adipocyte progenitors, as revealed by single nucleus RNAseq. Taken together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity.
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