Differential activation of JAK-STAT signaling reveals functional compartmentalization in Drosophila blood progenitors

  1. Diana Rodrigues
  2. Yoan Renaud
  3. K VijayRaghavan
  4. Lucas Waltzer  Is a corresponding author
  5. Maneesha S Inamdar  Is a corresponding author
  1. National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
  2. GReD (Genetics, Reproduction and Development Institute), INSERM 1103, CNRS 6293, University of Clermont Auvergne, France
  3. University of Clermont Auvergne, France
  4. Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India, India

Abstract

Blood cells arise from diverse pools of stem and progenitor cells. Understanding progenitor heterogeneity is a major challenge. The Drosophila larval lymph gland is a well-studied model to understand blood progenitor maintenance and recapitulates several aspects of vertebrate hematopoiesis. However in-depth analysis has focused on the anterior lobe progenitors (AP), ignoring the posterior progenitors (PP) from the posterior lobes. Using in situ expression mapping, developmental and transcriptome analysis we reveal PP heterogeneity and identify molecular-genetic tools to study this abundant progenitor population. Functional analysis shows that PP resist differentiation upon immune challenge, in a JAK-STAT-dependent manner. Upon wasp parasitism, AP downregulate JAK-STAT signaling and form lamellocytes. In contrast, we show that PP activate STAT92E and remain undifferentiated, promoting survival. Stat92E knockdown or genetically reducing JAK-STAT signaling permits PP lamellocyte differentiation. We discuss how heterogeneity and compartmentalization allow functional segregation in response to systemic cues and could be widely applicable.

Data availability

RNA-seq data has been deposited in GEO under the accession number GSE152416.All data generated or analysed during this study are included in the manuscript and supporting files.Source data files have been provided for Figures 1, 3, 4, 5, 6, 7 and Figure 1-figure supplement- 1, 2, Figure 4-figure supplement- 1, 2, Figure 5-figure supplement- 1, 2, Figure 7-figure supplement- 1

Article and author information

Author details

  1. Diana Rodrigues

    Department of Developmental Biology and Genetics, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    No competing interests declared.
  2. Yoan Renaud

    Development, GReD (Genetics, Reproduction and Development Institute), INSERM 1103, CNRS 6293, University of Clermont Auvergne, Clermont Ferrand, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4036-8315
  3. K VijayRaghavan

    Department of Developmental Biology and Genetics, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    K VijayRaghavan, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4705-5629
  4. Lucas Waltzer

    University of Clermont Auvergne, Clermont-Ferrand, France
    For correspondence
    lucas.waltzer@uca.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5361-727X
  5. Maneesha S Inamdar

    Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India, Bangalore, India
    For correspondence
    inamdar@jncasr.ac.in
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8243-2821

Funding

Indo-French Centre for the Promotion of Advanced Research

  • Maneesha S Inamdar

Science and Engineering Research Board

  • Maneesha S Inamdar

J C Bose Fellowship

  • Maneesha S Inamdar

Jawaharlal Nehru Centre for Advanced Scientific Research

  • Maneesha S Inamdar

Agence Nationale pour la Recherche and Fondation ARC

  • Lucas Waltzer

Indo-French Centre for the Promotion of Advanced Research

  • Lucas Waltzer

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

Reviewing Editor

  1. Jiwon Shim, Hanyang University, Republic of Korea

Publication history

  1. Received: July 24, 2020
  2. Accepted: February 16, 2021
  3. Accepted Manuscript published: February 17, 2021 (version 1)
  4. Version of Record published: March 1, 2021 (version 2)

Copyright

© 2021, Rodrigues 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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  1. Diana Rodrigues
  2. Yoan Renaud
  3. K VijayRaghavan
  4. Lucas Waltzer
  5. Maneesha S Inamdar
(2021)
Differential activation of JAK-STAT signaling reveals functional compartmentalization in Drosophila blood progenitors
eLife 10:e61409.
https://doi.org/10.7554/eLife.61409

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