1. Developmental Biology
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Fatty acid β-oxidation is required for the differentiation of larval hematopoietic progenitors in Drosophila

  1. Satish Kumar Tiwari
  2. Ashish Ganeshlalji Toshniwal
  3. Sudip Mandal
  4. Lolitika Mandal  Is a corresponding author
  1. Indian Institute of Science Education and Research Mohali, India
Research Article
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Cite this article as: eLife 2020;9:e53247 doi: 10.7554/eLife.53247

Abstract

Cell-intrinsic and extrinsic signals regulate the state and fate of stem and progenitor cells. Recent advances in metabolomics illustrate that various metabolic pathways are also important in regulating stem cell fate. However, our understanding of the metabolic control of the state and fate of progenitor cells is in its infancy. Using Drosophila hematopoietic organ: lymph gland, we demonstrate that Fatty Acid Oxidation (FAO) is essential for the differentiation of blood cell progenitors. In the absence of FAO, the progenitors are unable to differentiate and exhibit altered histone acetylation. Interestingly, acetate supplementation rescues both histone acetylation and the differentiation defects. We further show that the CPT1/whd (withered), the rate-limiting enzyme of FAO, is transcriptionally regulated by Jun-Kinase (JNK), which has been previously implicated in progenitor differentiation. Our study thus reveals how the cellular signaling machinery integrates with the metabolic cue to facilitate the differentiation program.

Article and author information

Author details

  1. Satish Kumar Tiwari

    Developmental Genetics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Ashish Ganeshlalji Toshniwal

    Developmental Genetics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Sudip Mandal

    Molecular Cell and Developmental Biology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Lolitika Mandal

    Developmental Genetics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
    For correspondence
    lolitika@iisermohali.ac.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7711-6090

Funding

Wellcome Trust DBT India Alliance (IA/S/17/1/503100)

  • Lolitika Mandal

CSIR

  • Satish Kumar Tiwari

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: November 1, 2019
  2. Accepted: June 11, 2020
  3. Accepted Manuscript published: June 12, 2020 (version 1)
  4. Version of Record published: July 9, 2020 (version 2)

Copyright

© 2020, Tiwari et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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