RRC ID 70818
Author Girard JR, Goins LM, Vuu DM, Sharpley MS, Spratford CM, Mantri SR, Banerjee U.
Title Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis.
Journal Elife
Abstract Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type-specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single-cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.
Volume 10
Published 2021-10-29
DOI 10.7554/eLife.67516
PII 67516
PMID 34713801
PMC PMC8610493
MeSH Animals DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Female Hematopoiesis* Hemocytes / metabolism* Hemolymph / metabolism* Juvenile Hormones / genetics* Juvenile Hormones / metabolism Larva / genetics Larva / growth & development Male
IF 7.08
Drosophila DGRC#114255