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