RUNX1B Expression Is Highly Heterogeneous and Distinguishes Megakaryocytic and Erythroid Lineage Fate in Adult Mouse Hematopoiesis

PLoS Genetics
Julia E DraperGeorges Lacaud

Abstract

The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct protein isoforms. The activities and specific relevance of these two promoters in adult hematopoiesis remain to be fully elucidated. Utilizing a dual reporter mouse model we demonstrate that the distal P1 promoter is broadly active in adult hematopoietic stem and progenitor cell (HSPC) populations. By contrast the activity of the proximal P2 promoter is more restricted and its upregulation, in both the immature Lineage- Sca1high cKithigh (LSK) and bipotential Pre-Megakaryocytic/Erythroid Progenitor (PreMegE) populations, coincides with a loss of erythroid (Ery) specification. Accordingly the PreMegE population can be prospectively separated into "pro-erythroid" and "pro-megakaryocyte" populations based on Runx1 P2 activity. Comparative gene expression analyses between Runx1 P2+ and P2- populations indicated that levels of CD34 expression cou...Continue Reading

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Citations

Jun 29, 2017·Bioinformatics·Arief GusnantoChristopher Pope
Jul 22, 2017·Blood·Alan B Cantor
Aug 23, 2019·FEBS Letters·Sara MenegattiValerie Kouskoff
Sep 7, 2019·Development·Renaud MevelGeorges Lacaud
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Carmen LanzillottiFernanda Martini

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Datasets Mentioned

BETA
GSE68958
GM

Methods Mentioned

BETA
flow cytometry
PCR
RNA-Seq
RNA Seq
FACS
ChIP-Seq
Assay
Illumina Sequencing

Software Mentioned

rVISTA
Gene Set Enrichment Analyses ( GSEA )
GSEA
UCSC Browser

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