Single-cell transcriptome maps of myeloid blood cell lineages inDrosophila

Abstract

SUMMARYDrosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells. Here, we used single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discovered novel hemocyte types, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identified the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. We unraveled similarities and differences between embryonically derived- and larval lymph gland hemocytes. Finally, the comparison of Drosophila lymph gland hemocytes and human immune cells highlights similarities between prohemocytes and hematopoietic stem cell, and between mature hemocytes and myeloid cells across species. Altogether, our study provides detailed insights on the development and evolution of hematopoiesis at single-cell resolution.

Differential activation of JAK-STAT signaling in blood cell progenitors reveals functional compartmentalization of theDrosophilalymph gland

“…On the other hand, Stat92E mutation causes premature progenitor differentiation in the primary lobe but not in the posterior lobes (Krzemien et al, 2007), suggesting important differences in regulation and function of these lobes as well as inherent differences within the progenitor pool. Along that line, a recent single-cell RNA sequencing analysis of the LG has identified novel hemocyte sub-populations and suggests a higher degree of blood cell progenitor heterogeneity than previously thought (Cho et al, 2020) . However the posterior lobes were excluded from this study and positional information is not retained in such single-cell sequencing analysis.…”

Single-cell analysis of mosquito hemocytes identifies signatures of immune cell subtypes and cell differentiation

“…populations (Severo et al, 2018;Kwon & Smith, 2019). In addition, we also define two populations of mosquito oenocytoids (clusters 7 and 8) that likely reflect immature and mature cell populations similar to orthologous crystal cell populations described in Drosophila (Tattikota et al, 2020;Cho et al, 2020;. The mature oenocytoids of Cluster 8 are denoted in part by the increased expression of lozenge, PPO1, pebbled, DNA J, MLF, Notch, and klumpfuss as previously described (Tattikota et al, 2020;Cho et al, 2020;Koranteng et al, 2020), as well as the increase in SCRB3 and SCRB9 which serve as a new marker of mosquito oenocytoids in our analysis.…”

“…In addition, we also define two populations of mosquito oenocytoids (clusters 7 and 8) that likely reflect immature and mature cell populations similar to orthologous crystal cell populations described in Drosophila (Tattikota et al, 2020;Cho et al, 2020;. The mature oenocytoids of Cluster 8 are denoted in part by the increased expression of lozenge, PPO1, pebbled, DNA J, MLF, Notch, and klumpfuss as previously described (Tattikota et al, 2020;Cho et al, 2020;Koranteng et al, 2020), as well as the increase in SCRB3 and SCRB9 which serve as a new marker of mosquito oenocytoids in our analysis. Despite these differences in cell maturation, the mosquito oenocytoid lineage is distinct from that of granulocytes and relies on the expression of lozenge to promote oenocytoid differentiation similar to its role in Drosophila crystal cells (Fossett et al, 2003;Waltzer et al, 2003).…”

“…Recently, the advent of single-cell sequencing (scRNA-seq) has continued to delineate and provide further resolution into new cell types and immune cell functions in mammals (Amara Korba et al, 2016;Szabo et al, 2019). In lesser studied invertebrates lacking adaptive immunity, single-cell technologies have enhanced descriptions of previously described cell types and have redefined cell complexity (Severo et al, 2018;Cattenoz et al, 2020;Cho et al, 2020;Raddi et al, 2020;Tattikota et al, 2020).…”

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

“…Of the 13,000 genes (total number of genes > 17,500) represented in this microarray, they were able to identify 2500 with significantly enriched expression in hemocytes, notably genes encoding integrins, peptidoglycan recognition proteins (PGRPs), scavenger receptors, lectins, cell adhesion molecules and serine proteases. Interestingly, several single cell transcriptomic analyses have revealed the degree of heterogeneity of Drosophila hemocyte populations, but they did not characterize the full repertoire of genes expressed in hemocytes [36][37][38][39].…”