An integrated single cell and spatial transcriptomic map of human white adipose tissue

Abstract

To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.

A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion

“…The SFRP4+ cluster was characterized by high expression of Secreted frizzled-related proteins 2 and 4 (SFRP2 and SFRP4) (Figures 3A, S3I), and aligned with a subpopulation of the published human AT atlas 7,8 (Figure S3J). SFRPs are inhibitors of the Wnt signaling pathway, a key regulator of adipocyte differentiation 36 , and SFRP2-4, in particular, were shown to be upregulated in obesity, especially in visceral WAT 37 .…”

“…These are F3, CLEC11A, GDF10, MGP, and INMT (Figure 3A, S3A). Recently, in their single cell atlas of human AT, Emont and colleagues followed by Massier and colleagues identified a cluster that is characterized by enriched expression of EPHA3, and that exhibits substantial similarities to the murine Aregs 7,8 . Notably, EPHA3 is specifically expressed by the HHIP+ cells that we identified in our analyses (Figure S3A), further supporting its alignment with mouse Aregs.…”

“…This hypothesis was initially supported by studies showing that SVF cells from human SC AT proliferated and differentiated more potently than those of visceral fat 6 . More recently, comprehensive singlecell transcriptomic (scRNA-seq) atlases of whole human AT, as well as previously published studies, have provided insights into the heterogeneity of human ASPCs (hASPCs) [7][8][9][10] . However, these scRNA-seq studies focused on the two most studied ATs: SC and OM.…”

“…In contrast, Icam1+ (or Aoc3+) cells can be classified as pre-adipocytes (PreAs), showing a lower proliferation capacity and a more committed adipogenic state compared with ASCs. Finally, a subset of cells characterized by high expression of F3 were termed adipogenesis-regulatory cells (Aregs) due to their ability to regulate the differentiation capacity of other ASPCs [7][8][9][11][12][13][14][15][16][17][18] . A similar level of phenotypic characterization of hASPC populations is however still lacking, likely reflecting the challenge of having access to and/or gathering enough human biopsy material.…”

Erkenntnisse aus der Fettgewebsforschung

“…Mit dem Aufkommen der Single-Cell-RNA-Sequencing-Technologie (scRNA-seq) konnten auch im humanen Fettgewebe neue Subtypen spezifischer Zellen in einem unvoreingenommenen Ansatz in der stromal-vaskulären Zellfraktion des Gewebes untersucht werden 14 15 . Das Fettgewebe stellt eine besondere Herausforderung für die Anwendung von scRNA-seq dar, da Adipozyten mit dieser Methode nicht detektiert werden.…”