Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Diverse repertoire of human adipocyte subtypes develops from transcriptionally distinct mesenchymal progenitor cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Unfolding of monomeric lipoprotein lipase by ANGPTL4: Insight into the regulation of plasma triglyceride metabolism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Galnt11 regulates kidney function by glycosylating the endocytosis receptor megalin to modulate ligand binding

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. N-acyl taurines are endogenous lipid messengers that improve glucose homeostasis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Early sarcomere and metabolic defects in a zebrafish pitx2c cardiac arrhythmia model

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Mode of action of quinoline antimalarial drugs in red blood cells infected by Plasmodium falciparum revealed in vivo

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. An anti-inflammatory phenotype in visceral adipose tissue of old lean mice, augmented by exercise

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Dysregulated autophagy in muscle precursor cells from humans with type 2 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • So Yun Min
  • Anand Desai
  • Zinger Yang
  • Agastya Sharma
  • Tiffany DeSouza
  • Ryan M J Genga
  • Alper Kucukural
  • Lawrence M Lifshitz
  • Søren Nielsen
  • Camilla Scheele
  • René Maehr
  • Manuel Garber
  • Silvia Corvera
Vis graf over relationer

Single-cell sequencing technologies have revealed an unexpectedly broad repertoire of cells required to mediate complex functions in multicellular organisms. Despite the multiple roles of adipose tissue in maintaining systemic metabolic homeostasis, adipocytes are thought to be largely homogenous with only 2 major subtypes recognized in humans so far. Here we report the existence and characteristics of 4 distinct human adipocyte subtypes, and of their respective mesenchymal progenitors. The phenotypes of these distinct adipocyte subtypes are differentially associated with key adipose tissue functions, including thermogenesis, lipid storage, and adipokine secretion. The transcriptomic signature of "brite/beige" thermogenic adipocytes reveals mechanisms for iron accumulation and protection from oxidative stress, necessary for mitochondrial biogenesis and respiration upon activation. Importantly, this signature is enriched in human supraclavicular adipose tissue, confirming that these cells comprise thermogenic depots in vivo, and explain previous findings of a rate-limiting role of iron in adipose tissue browning. The mesenchymal progenitors that give rise to beige/brite adipocytes express a unique set of cytokines and transcriptional regulators involved in immune cell modulation of adipose tissue browning. Unexpectedly, we also find adipocyte subtypes specialized for high-level expression of the adipokines adiponectin or leptin, associated with distinct transcription factors previously implicated in adipocyte differentiation. The finding of a broad adipocyte repertoire derived from a distinct set of mesenchymal progenitors, and of the transcriptional regulators that can control their development, provides a framework for understanding human adipose tissue function and role in metabolic disease.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind116
Udgave nummer36
Sider (fra-til)17970-17979
Antal sider10
ISSN0027-8424
DOI
StatusUdgivet - 3 sep. 2019

Bibliografisk note

Copyright © 2019 the Author(s). Published by PNAS.

ID: 59099807