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Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

ABSTRACT: Here we provide scRNAseq data from the stromal vascular fraction of adult (8 weeks) and adolescent (2 weeks) murine inguinal subcutaneous white adipose tissue. This allows studying cellular composition and cellular heterogeneity within subcutaneous fat.

ORGANISM(S): Mus musculus

PROVIDER: GSE164350 | GEO | 2021/01/07

REPOSITORIES: GEO

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Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.

Project description:Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

| S-EPMC7952576 | biostudies-literature

A non-cell autonomous mechanism of beige adipocyte renaissance in subcutaneous adipose tissue

Project description:Two types of UCP1 positive cells-brown and beige adipocytes exist in mammals. Beige adipocytes are very plastic, and can be dynamically regulated by environment.Beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue (iWAT) lost thermogenic gene expression and multilocular morphology at adult stage, but cold could restore their “beigeing” characteristics, a phenomenon termed as beige adipocyte renaissance. Our results showed that beige cell maintenance and renaissance in adult mice were regulated by cAMP and HDAC4 signaling in white adipocytes non-cell autonomously. Genetic modulations of various components of this cAMP-HDAC4 cascade (e.g. LKB1) led to persistent browning and reduced adiposity independent of thermogenesis. To further study the mechanisms of beige adipocytes maintenance, we performed RNA-seq with samples from inguinal white adipose tissues of WT, AdipoqCre LKB1 F/F, and AdipoqCre LKB1 F/F; HDAC4 F/F mice.Our studies will move the beige adipocyte field forward and attract clinical applications to target beige adipocyte renaissance.

2018-02-14 | GSE85335 | GEO

Transcriptomic profiling of subcutaneous white adipose tissue with selective ablation of Bmal1 at ambient and cold condition

Project description:Mice with beige fat-selective ablation of Bmal1 were generated by crossing Bmal1fl/fl with Prrx1-Cre transgenics. Inguinal subcutaneous adipsoe tissues were collected under ambient temperature at 220C or cold acclimations at 10oC for two weeks.

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Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

Project description:Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

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RNA-Seq of subcutaneous inguinal white fat of Hlx transgenic mice and littermate controls.

Project description:RNA-Seq of subcutaneous inguinal white fat of Hlx transgenic mice and littermate controls.

2017-08-11 | GSE78143 | GEO

Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development

Project description:We performed a large-scale single cell transcriptomic (scRNA-seq) and epigenomic (snATAC-seq) characterization of cellular subtypes (adipose stromal cells (ASC) and adipocyte nuclei) during inguinal WAT (subcutaneous; iWAT) development in mice, capturing the early postnatal period (postnatal days (PND) 06 and 18) through adulthood (PND56).

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Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in mice

Project description:We sequenced strand-specific rRNA-depleted librairies performed from total RNAs isolated from subcutaneous inguinal fat pads of three 2-week-old wild-type female mice and three 2-week-old Egr1-deficient female mice.

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Molecular basis of beige adipocyte maintenance

Project description:Mature adipocytes from Inguinal WAT of CL316,243-treated Ucp1Cre/+;Rosa26-LSL-GFP mice were isolated and GFP+ adipocytes were collected and subjected to transcriptome profiling by RNA-seq.

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Egr1 loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue.

Project description:In mice, exercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production. This browning process is associated with an increased expression of the key thermogenic mitochondrial uncoupling protein 1, Ucp1. Egr1 transcription factor has been described as a regulator of white and beige differentiation programs, and Egr1 depletion is associated with a spontaneous increase of subcutaneous white adipose tissue browning, in absence of external stimulation. Here, we demonstrate that Egr1 mutant mice exhibit a restrained Ucp1 expression specifically increased in subcutaneous fat, resulting in a metabolic shift to a more brown-like, oxidative metabolism, which was not observed in other fat depots. In addition, Egr1 is necessary and sufficient to promote white and alter beige adipocyte differentiation of mouse stem cells. These results suggest that modulation of Egr1 expression could represent a promising therapeutic strategy to increase energy expenditure and to restrain obesity-associated metabolic disorders.

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Ablation of adipocyte BCL6 enhances subcutaneous adiposity and insulin sensitivity [ChIP-seq]

Project description:In adipocyte-specific knockout mice (Bcl6AKO), we found that Bcl6 deletion results in strikingly increased inguinal but not perigonadal adipocyte size and tissue mass in addition to marked insulin sensitivity. Genome-wide DNA binding and RNA expression analyses revealed that BCL6 controls gene networks involved in cell growth and fatty acid biosynthesis. Thus, our studies identify BCL6 as a negative regulator of subcutaneous adipose tissue expansion and metabolic health.

2019-02-26 | GSE113407 | GEO

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