PT - JOURNAL ARTICLE AU - Diana Rodrigues AU - Yoan Renaud AU - K. VijayRaghavan AU - Lucas Waltzer AU - Maneesha S. Inamdar TI - Differential activation of JAK-STAT signaling in blood cell progenitors reveals functional compartmentalization of the <em>Drosophila</em> lymph gland AID - 10.1101/2020.07.26.219717 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.26.219717 4099 - http://biorxiv.org/content/early/2020/07/26/2020.07.26.219717.short 4100 - http://biorxiv.org/content/early/2020/07/26/2020.07.26.219717.full AB - 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 progenitors located in lymph gland anterior lobes (AP), ignoring the progenitors from the posterior lobes (PP). Using in situ expression mapping 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. Stat92E knockdown in PP 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.Highlights We provide an in situ and transcriptome map of larval blood progenitors Posterior lymph gland progenitors are refractory to immune challenge STAT activation after wasp parasitism maintains posterior progenitorsCompeting Interest StatementThe authors have declared no competing interest.