Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis

eLife

Shreya R Mantri¹  Carrie M Spratford¹  Juliet R Girard¹  Lauren M Goins¹  Dung M Vuu¹  Mark S Sharpley¹  Utpal Banerjee² 

[1] Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States;Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States;Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States;Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States;Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States;

关键词: hematopoiesis;    crystal cells;    lymph gland;    blood progenitors;    stem cells;    intermediate progenitors;    D. melanogaster;   

DOI  :  10.7554/eLife.67516

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY