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

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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.

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All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures (that includes GraphPad or excel representations of the quantitative analyses).

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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.
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.
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.
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.

"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.

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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.