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

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...

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Autores principales:	Juliet R Girard, Lauren M Goins, Dung M Vuu, Mark S Sharpley, Carrie M Spratford, Shreya R Mantri, Utpal Banerjee
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	hematopoiesis crystal cells lymph gland blood progenitors stem cells intermediate progenitors Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b5c668a8e4d744bdbdb753ddb87caae0
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spelling	oai:doaj.org-article:b5c668a8e4d744bdbdb753ddb87caae02021-11-23T14:48:54ZPaths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis10.7554/eLife.675162050-084Xe67516https://doaj.org/article/b5c668a8e4d744bdbdb753ddb87caae02021-10-01T00:00:00Zhttps://elifesciences.org/articles/67516https://doaj.org/toc/2050-084XMechanistic 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.Juliet R GirardLauren M GoinsDung M VuuMark S SharpleyCarrie M SpratfordShreya R MantriUtpal BanerjeeeLife Sciences Publications Ltdarticlehematopoiesiscrystal cellslymph glandblood progenitorsstem cellsintermediate progenitorsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hematopoiesis crystal cells lymph gland blood progenitors stem cells intermediate progenitors Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	hematopoiesis crystal cells lymph gland blood progenitors stem cells intermediate progenitors Medicine R Science Q Biology (General) QH301-705.5 Juliet R Girard Lauren M Goins Dung M Vuu Mark S Sharpley Carrie M Spratford Shreya R Mantri Utpal Banerjee Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
description	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.
format	article
author	Juliet R Girard Lauren M Goins Dung M Vuu Mark S Sharpley Carrie M Spratford Shreya R Mantri Utpal Banerjee
author_facet	Juliet R Girard Lauren M Goins Dung M Vuu Mark S Sharpley Carrie M Spratford Shreya R Mantri Utpal Banerjee
author_sort	Juliet R Girard
title	Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
title_short	Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
title_full	Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
title_fullStr	Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
title_full_unstemmed	Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
title_sort	paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/b5c668a8e4d744bdbdb753ddb87caae0
work_keys_str_mv	AT julietrgirard pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis AT laurenmgoins pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis AT dungmvuu pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis AT markssharpley pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis AT carriemspratford pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis AT shreyarmantri pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis AT utpalbanerjee pathsandpathwaysthatgeneratecelltypeheterogeneityanddevelopmentalprogressioninhematopoiesis
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Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis

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