Nfix expression critically modulates early B lymphopoiesis and myelopoiesis

PloS One
Caitríona O'ConnorKaren Keeshan

Abstract

The commitment of stem and progenitor cells toward specific hematopoietic lineages is tightly controlled by a number of transcription factors that regulate differentiation programs via the expression of lineage restricting genes. Nuclear factor one (NFI) transcription factors are important in regulating hematopoiesis and here we report an important physiological role of NFIX in B- and myeloid lineage commitment and differentiation. We demonstrate that NFIX acts as a regulator of lineage specification in the haematopoietic system and the expression of Nfix was transcriptionally downregulated as B cells commit and differentiate, whilst maintained in myeloid progenitor cells. Ectopic Nfix expression in vivo blocked early B cell development stage, coincident with the stage of its downregulation. Furthermore, loss of Nfix resulted in the perturbation of myeloid and lymphoid cell differentiation, and a skewing of gene expression involved in lineage fate determination. Nfix was able to promote myeloid differentiation of total bone marrow cells under B cell specific culture conditions but not when expressed in the hematopoietic stem cell (HSPC), consistent with its role in HSPC survival. The lineage choice determined by Nfix correlated...Continue Reading

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Citations

Feb 13, 2018·Stem Cells·Trent HallShannon McKinney-Freeman
Nov 14, 2018·Nature Genetics·Salam A AssiConstanze Bonifer
Oct 18, 2020·In Vitro Cellular & Developmental Biology. Animal·Xianglun CuiWenhua Xu
Mar 5, 2021·Ocular Immunology and Inflammation·John A GonzalesThuy Doan
Jul 20, 2021·Frontiers in Cell and Developmental Biology·Wen-Bin ZhengXing-Quan Zhu

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

GSEA
FlowJo
HemaExplorer
GraphPad Prism
Treestar
Affymetrix
GraphPad
GenePattern
Fluidigm

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