Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population
Autor: | Anika Böttcher, Matthias Heinig, Ahmed Elagamy Mohamed Mahmoud Khalil, Lisa Suwandhi, Tobias Wiedemann, Philippe Schmitt-Kopplin, Irem Altun, Martin Elsner, Ingo Burtscher, Siegfried Ussar, Silke S. Heinzmann, David S. Fischer, Ines Pramme-Steinwachs, Viktorian Miok, Andreas Israel, Christina Lindner, Heiko Lickert, Thomas Walzthoeni, Alexander Braun, Ruth Karlina, Fabian J. Theis |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Adipocytes White Cell General Physics and Astronomy Adipose tissue White adipose tissue Mice chemistry.chemical_compound 0302 clinical medicine Adipocyte Adipocytes Beige Cells Cultured Uncoupling Protein 1 Mice Knockout Mice Inbred BALB C education.field_of_study Multidisciplinary Cell Differentiation Stromal vascular fraction ddc Mechanisms of disease medicine.anatomical_structure Differentiation Single-Cell Analysis Cell type medicine.medical_specialty Stromal cell Amino Acid Transport System y+ Science Adipose Tissue White Population Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine medicine Animals Obesity education Base Sequence Sequence Analysis RNA General Chemistry Adipose Tissue Beige Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry 030217 neurology & neurosurgery |
Zdroj: | Nat. Commun. 12:1588 (2021) Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) |
ISSN: | 2041-1723 |
Popis: | 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. Adipose tissue is composed of a variety of cell types, including adipocyte precursor populations, that contribute to adipose tissue function upon differentiation. Here, using scRNA-sequencing of adolescent and adult mouse subcutaneous adipose tissue, the authors identify an Asc-1 positive preadipocyte population that is enriched in adolescent subcutaneous fat and demonstrate that loss of Asc-1 triggers spontaneous beige adipocyte differentiation. |
Databáze: | OpenAIRE |
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