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BMPER: a novel adipose progenitor marker and adipogenic modulator

ABSTRACT: BMPER: a novel adipose progenitor marker and adipogenic modulator

PROVIDER: PRJNA887823 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21834918.fastq.gz	Fastqsanger.gz
	SRR21834919.fastq.gz	Fastqsanger.gz
	SRR21834920.fastq.gz	Fastqsanger.gz
	SRR21834921.fastq.gz	Fastqsanger.gz
	SRR21834922.fastq.gz	Fastqsanger.gz

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BMPER: a novel adipose progenitor marker and adipogenic modulator

Project description:We used single cell sequencing to identify sex and diet-specific differences in visceral adipose progenitor cells (APCs) and to discover new APC markers and adipogenic modulators. We identified the major clusters that were previously identified by other studies both in humans and mice with the notable difference being in the mesothelial cluster, which was more abundant in humans than mice. We found that diet/obesity resulted in minor differences in the proportions of major clusters in humans but increased immune cells in male mice with high fat feeding. Most importantly, we identified BMPER as a novel marker of APCs both in humans and mice and revealed its pro-adipogenic property.

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Project description:Background: Mature adipocytes are notoriously difficult to study ex vivo and alternative cell culture systems have therefore been developed. One of the most common models are human adipose progenitor cells (hAPCs). Unfortunately, these display replicative senescence after prolonged culture conditions, which limits their use in mechanistic studies. Methods: Herein, we knocked in human telomerase reverse transcriptase (TERT) into the AAVS1 locus of CD55+ hAPCs derived from abdominal subcutaneous adipose tissue and characterized the cells before and after differentiation into adipocytes. Results: Immortalized TERT-hAPCs retained proliferative and adipogenic capacities comparable to those of early-passage wild type hAPCs for >80 passages. In line with this, our integrative transcriptomic and proteomic analyses revealed that TERT-hAPCs displayed robust adipocyte expression profiles. This was confirmed by functional analyses of lipid turnover where TERT-hAPCs exhibited pronounced responses to insulin and pro-lipolytic stimuli such as isoprenaline, dibutyrul cAMP and tumor necrosis factor alpha. In addition, TERT-hAPCs could be readily cultured in both standard 2D and 3D-cultures and proteomic analyses revealed that the spheroid culture conditions improved adipogenesis. Conclusion: Through descriptive and functional studies, we demonstrate that immortalization of human CD55+ hAPCs is feasible and results in cells with stable proliferative and adipogenic capacities over multiple passages. As these cells are cryopreservable, they provide the additional advantage over primary cells of allowing repeated studies in both 2D and 3D model systems with the same genetic background.

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