PRDM16 Maintains Homeostasis of the Intestinal Epithelium by Controlling Region-Specific Metabolism

Cell Stem Cell. 2019 Dec 5;25(6):830-845.e8. doi: 10.1016/j.stem.2019.08.017. Epub 2019 Sep 26.


Metabolic pathways dynamically regulate tissue development and maintenance. However, the mechanisms that govern the metabolic adaptation of stem or progenitor cells to their local niche are poorly understood. Here, we define the transcription factor PRDM16 as a region-specific regulator of intestinal metabolism and epithelial renewal. PRDM16 is selectively expressed in the upper intestine, with enrichment in crypt-resident progenitor cells. Acute Prdm16 deletion in mice triggered progenitor apoptosis, leading to diminished epithelial differentiation and severe intestinal atrophy. Genomic and metabolic analyses showed that PRDM16 transcriptionally controls fatty acid oxidation (FAO) in crypts. Expression of this PRDM16-driven FAO program was highest in the upper small intestine and declined distally. Accordingly, deletion of Prdm16 or inhibition of FAO selectively impaired the development and maintenance of upper intestinal enteroids, and these effects were rescued by acetate treatment. Collectively, these data reveal that regionally specified metabolic programs regulate intestinal maintenance.

Keywords: PRDM16; apoptosis; differentiation; duodenum; fatty acid oxidation; intestinal stem cell; intestine; metabolism; transit amplifying cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Intestinal Mucosa / metabolism*
  • Male
  • Mass Spectrometry
  • Mice
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Prdm16 protein, mouse
  • Transcription Factors