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

Abstract
Data availability
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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.

Data availability

Sequencing data have been deposited in GEO under Accession Code GSE168823Complete Source Data are provided

The following data sets were generated

(2021) Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis
NCBI Gene Expression Omnibus GSE168823.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168823

Article and author information

Author details

Juliet R Girard

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-8274-2136
Lauren M Goins

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Dung M Vuu

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Mark S Sharpley

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Carrie M Spratford

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Shreya R Mantri

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Utpal Banerjee

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

For correspondence
banerjee@mbi.ucla.edu

Competing interests
Utpal Banerjee, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-6247-0284

Funding

National Heart, Lung, and Blood Institute (R01-HL067395)

Utpal Banerjee

National Cancer Institute (R01-CA217608)

Utpal Banerjee

National Heart, Lung, and Blood Institute (T32-HL69766)

Juliet R Girard

National Institute of General Medical Sciences (K12-GM106996)

Juliet R Girard

National Cancer Institute (T32-CA009056)

Lauren M Goins

National Heart, Lung, and Blood Institute (T32-HL863458)

Carrie M Spratford

Center for Global Mentoring at UCLA-DOE Institute for Genomics & Proteomics

Dung M Vuu

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

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.