Mutant KLF1 in Adult Anemic Nan Mice Leads to Profound Transcriptome Changes and Disordered Erythropoiesis

Scientific Reports
Danitza NéborLuanne L Peters

Abstract

Anemic Nan mice carry a mutation (E339D) in the second zinc finger of erythroid transcription factor KLF1. Nan-KLF1 fails to bind a subset of normal KLF1 targets and ectopically binds a large set of genes not normally engaged by KLF1, resulting in a corrupted fetal liver transcriptome. Here, we performed RNAseq using flow cytometric-sorted spleen erythroid precursors from adult Nan and WT littermates rendered anemic by phlebotomy to identify global transcriptome changes specific to the Nan Klf1 mutation as opposed to anemia generally. Mutant Nan-KLF1 leads to extensive and progressive transcriptome corruption in adult spleen erythroid precursors such that stress erythropoiesis is severely compromised. Terminal erythroid differentiation is defective in the bone marrow as well. Principle component analysis reveals two major patterns of differential gene expression predicting that defects in basic cellular processes including translation, cell cycle, and DNA repair could contribute to disordered erythropoiesis and anemia in Nan. Significant erythroid precursor stage specific changes were identified in some of these processes in Nan. Remarkably, however, despite expression changes in large numbers of associated genes, most basic ce...Continue Reading

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Mar 29, 2019·PloS One·Ileana CantúThamar B van Dijk
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Datasets Mentioned

BETA
GSE71396
PRJNA432205

Methods Mentioned

BETA
RNAseq
PCA
flow cytometry
PCR

Software Mentioned

Biosystems Sequencing Analysis
STAR Aligner
Applied
RNAseq
DAVID
NIS
DESeq2
LSRFortessa
Elements Documentation imaging
Gencode

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