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

Elife. 2021 Feb 17;10:e61409. doi: 10.7554/eLife.61409.

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 and 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.

Keywords: D. melanogaster; Drosophila hematopoiesis; JAK-STAT pathway; developmental biology; heterogeneous progenitors; immune response; lymph gland development; posterior lobe markers; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / parasitology
  • Hematopoiesis / physiology
  • Hemocytes / immunology
  • Hemocytes / metabolism
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • Larva / immunology
  • Larva / parasitology
  • Lymph Nodes / physiology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism*
  • Signal Transduction
  • Stem Cells
  • Wasps / physiology

Substances

  • STAT Transcription Factors
  • Janus Kinases

Associated data

  • GEO/GSE152416

Grant support

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