Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity

Hyun Cheol Roh, Linus T.Y. Tsai, Mengle Shao, Danielle Tenen, Yachen Shen, Manju Kumari, Anna Lyubetskaya, Christopher Jacobs, Brian Dawes, Rana K Gupta, Evan D. Rosen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Beige and brown adipocytes generate heat in response to reductions in ambient temperature. When warmed, both beige and brown adipocytes exhibit morphological “whitening,” but it is unknown whether or to what extent this represents a true shift in cellular identity. Using cell-type-specific profiling in vivo, we uncover a unique paradigm of temperature-dependent epigenomic plasticity of beige, but not brown, adipocytes, with conversion from a brown to a white chromatin state. Despite this profound shift in cellular identity, warm whitened beige adipocytes retain an epigenomic memory of prior cold exposure defined by an array of poised enhancers that prime thermogenic genes for rapid response during a second bout of cold exposure. We further show that a transcriptional cascade involving glucocorticoid receptor and Zfp423 can drive warm-induced whitening of beige adipocytes. These studies identify the epigenomic and transcriptional bases of an extraordinary example of cellular plasticity in response to environmental signals. Both beige and brown adipocytes “whiten” upon warming. Roh et al. elegantly show that beige, but not brown, adipocytes undergo temperature-dependent reprogramming between brown- and white-like states, while retaining epigenomic memory of prior cold exposure. A transcriptional cascade underlies this plasticity response to environmental signals.

Original languageEnglish (US)
JournalCell Metabolism
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Brown Adipocytes
Epigenomics
Temperature
Glucocorticoid Receptors
Chromatin
Hot Temperature
Beige Adipocytes
Genes

Keywords

  • adipocyte
  • beige
  • brown
  • epigenome
  • epigenomic memory
  • glucocorticoid receptor
  • reprogramming
  • transcriptome
  • white
  • Zfp423

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Roh, H. C., Tsai, L. T. Y., Shao, M., Tenen, D., Shen, Y., Kumari, M., ... Rosen, E. D. (Accepted/In press). Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity. Cell Metabolism. https://doi.org/10.1016/j.cmet.2018.03.005

Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity. / Roh, Hyun Cheol; Tsai, Linus T.Y.; Shao, Mengle; Tenen, Danielle; Shen, Yachen; Kumari, Manju; Lyubetskaya, Anna; Jacobs, Christopher; Dawes, Brian; Gupta, Rana K; Rosen, Evan D.

In: Cell Metabolism, 01.01.2018.

Research output: Contribution to journalArticle

Roh, HC, Tsai, LTY, Shao, M, Tenen, D, Shen, Y, Kumari, M, Lyubetskaya, A, Jacobs, C, Dawes, B, Gupta, RK & Rosen, ED 2018, 'Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity', Cell Metabolism. https://doi.org/10.1016/j.cmet.2018.03.005
Roh, Hyun Cheol ; Tsai, Linus T.Y. ; Shao, Mengle ; Tenen, Danielle ; Shen, Yachen ; Kumari, Manju ; Lyubetskaya, Anna ; Jacobs, Christopher ; Dawes, Brian ; Gupta, Rana K ; Rosen, Evan D. / Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity. In: Cell Metabolism. 2018.
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