“Multiple human adipocyte subtypes and mechanisms of their development”

Sy, Min; Desai, Anand; Yang, Zinger; Sharma, Agastya; Rm, Genga; Küçükural, Alper; Lifshitz, Lawrence M.; Maehr, René; Garber, Manuel; Corvera, Silvia

doi:10.1101/537464

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…2b). This finding aligns with previous studies associating TRHDE-AS1 with human adipocyte tissue development 27 . However, our analysis also reveals three lncRNAs, namely LINC01060 , RP11-231C18.3 , and RP11-1017G21.4 , which exhibited significantly high specificity scores in basal cells, NKT (natural killer T) cells, and mucosal cells, respectively.…”

Section: Resultssupporting

confidence: 93%

Landscape and functional repertoires of long noncoding RNAs in the pan-cancer tumor microenvironment using single-nucleus total RNA sequencing

Fan,

Ni,

Chen

et al. 2023

Preprint

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Intratumor heterogeneity (ITH) plays crucial roles in tumor progression. However, the atlas of long noncoding RNAs (lncRNAs) in the context of ITH across multiple cancer types remains largely unexplored. Here, we analyze over 800,000 cells from ten different cancer types generated from the random-primed single-nucleus total RNA sequencing and provide a systematic landscape of lncRNAs in tumor microenvironment (TME) and malignant programs. Our study employe a robust cell annotation pipeline called scAnnotation, which allows us to identify 39 distinct cell types within the pan-cancer TME. By applying stringent criteria, we identify thousands of reliable marker genes, including both mRNAs and lncRNAs. Next, we identify sets of cell type-specific lncRNA-mRNA pairs by our LncPairs algorithm. Moreover, we identify nine expression meta-programs (MPs) associated with diverse biological processes in malignant cells across multiple cancer types. MP-specific lncRNA-transcription factor (TF) regulatory networks are further constructed and key lncRNAs and regulons that exert control over MP-specific gene expression are identified. The comprehensive atlas of lncRNAs in the pan-cancer context, coupled with the bioinformatics tools tailored for the random-primed datasets, is expected to accelerate advancements in the field of lncRNA research at the single-cell resolution.

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Section: Resultssupporting

confidence: 93%

Landscape and functional repertoires of long noncoding RNAs in the pan-cancer tumor microenvironment using single-nucleus total RNA sequencing

Fan,

Ni,

Chen

et al. 2023

Preprint

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“…One would hypothesize that decreased adipose tissue mass in ARC −/− mice would have resulted in improved insulin sensitivity and glucose tolerance, but we did not observe such improvements in this study. Although studies have shown that ARC is expressed in white and brown adipose tissue depots (Rosell et al 2014, Liu et al 2015, Min et al 2019, relatively little is known about the role of ARC in adipose tissue. Thus, it is possible that loss of ARC in adipose tissue impacts glucose homeostasis.…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

Loss of apoptosis repressor with caspase recruitment domain (ARC) worsens high fat diet-induced hyperglycemia in mice

Templin

Schmidt

Hogan

et al. 2021

Journal of Endocrinology

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Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous inhibitor of cell death signaling that is expressed in insulin-producing β-cells. ARC has been shown to reduce β-cell death in response to diabetogenic stimuli in vitro, but its role in maintaining glucose homeostasis in vivo has not been fully established. Here we examined whether loss of ARC in FVB background mice exacerbates high fat diet (HFD)-induced hyperglycemia in vivo over 24 weeks. Prior to commencing 24-week HFD, ARC-/- mice had lower body weight than wild type (WT) mice. This body weight difference was maintained until the end of the study and was associated with decreased epididymal and inguinal adipose tissue mass in ARC-/- mice. Non-fasting plasma glucose was not different between ARC-/- and WT mice prior to HFD feeding, and ARC-/- mice displayed a greater increase in plasma glucose over the first 4 weeks of HFD. Plasma glucose remained elevated in ARC-/- mice after 16 weeks of HFD feeding, at which time it had returned to baseline in WT mice. Following 24 weeks of HFD, non-fasting plasma glucose in ARC-/- mice returned to baseline and was not different from WT mice. At this final time point, no differences in plasma glucose or insulin were observed under fasted conditions or following IV glucose administration between genotypes. However, HFD-fed ARC-/- mice exhibited significantly decreased β-cell area compared to WT mice. Thus, ARC deficiency delays, but does not prevent, metabolic adaptation to HFD feeding in mice, worsening transient HFD-induced hyperglycemia.

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Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome

Kahn

Wang

Lee

2019

Journal of Clinical Investigation

452

364

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ipocytes have higher expression of short stature homeobox 2 (Shox2) and glypican-4 (GPC4), which repress lipolysis and insulin sensitivity, respectively (24-27), whereas visceral adipose tissue has higher levels of HoxC8 and HoxA5, which regulate browning and adipogenesis (28, 29). In addition to subcutaneous and visceral fat, WAT in other depots may have distinct functions and effects on metabolism. White adipocytes within dermal layers are developmentally distinct from subcutaneous WAT (30) and play roles in wound healing, hair development, and pathogen resistance (31). Bone marrow adipose tissue (MAT) is also a distinct depot and includes two distinct subtypes (32): constitutive MAT (cMAT), concentrated in the distal skeletal bones, and regulated MAT (rMAT), which is diffusely distributed in the spine and proximal limb bones and is regulated in response to environmental factors (33, 34). MAT plays important roles in bone metabolism and osteoblastic activity (35). Interestingly, MAT is not depleted in calorically deficient states and may be a major source of circulating adiponectin (36, 37). Intra-depot heterogeneity in adipose tissue. A growing body of evidence indicates that adipocytes, even within a single fat pad, are heterogeneous in nature both genetically and metabolically (Figure 1B and refs. 38-41). This was initially suggested by a bimodal size distribution of adipocytes in mice with fat-specific ablation of the insulin receptor or hormone-sensitive lipase (HSL) (42, 43). Recent studies using clonal cell analysis and single-cell RNA-Seq further highlight this heterogeneity. Thus, white preadipocytes with low levels of CD9 are more adipogenic, whereas preadipocytes with high CD9 are more profibrotic and proinflammatory (44). By combining clonal analysis and lineage tracing, Lee et al. identified at least three functionally and developmentally distinct subpopulations of white preadipocytes in mice characterized by unique gene expression profiles and high expression of the marker genes Wilms tumor-1 (Wt1), transgelin, and myxovirus-1 (Mx1), termed types 1-3, respectively (45). Likewise, single-cell transcriptomic profiling of human preadipocytes and mesenchymal progenitor cells (46) has identified up to four adipocyte subtypes, including a beige/brite thermogenic subtype and a subtype specialized for leptin secretion.

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“Multiple human adipocyte subtypes and mechanisms of their development”

Cited by 3 publications

References 60 publications

Landscape and functional repertoires of long noncoding RNAs in the pan-cancer tumor microenvironment using single-nucleus total RNA sequencing

Landscape and functional repertoires of long noncoding RNAs in the pan-cancer tumor microenvironment using single-nucleus total RNA sequencing

Loss of apoptosis repressor with caspase recruitment domain (ARC) worsens high fat diet-induced hyperglycemia in mice

Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome

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