The Effects of TET2-Deficiency on Neutrophil Gene Expression and Function
type: CreativeWork
description: Background: Clonal hematopoiesis of indeterminate potential (CHIP), a potential precursor to myelodysplastic syndrome (MDS), affects over 10% of adults over 65. Loss-of-function ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) variants are common in CHIP and associate with epigenetic dysregulation, inflammation, and cardiovascular disease. Although neutrophils are sensitive to epigenetic dysregulation and contribute to many cardiovascular diseases, the effects of TET2-deficiency on neutrophils have not been characterized. We hypothesize that TET2-deficiency dysregulates gene expression and function in neutrophils. Methods: With informed consent and ethics approval, serum and peripheral blood (PB) were collected from CHIP subjects and controls. RNA was extracted from whole PB and mRNA expression of two representative neutrophil granule genes, myeloperoxidase (MPO) and lactotransferrin (LTF), were assessed using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). MPO and LTF serum protein titers were quantified with enzyme-linked immunosorbent assays (ELISA). Additionally, the Tet2flox/flox Vav-iCre mouse model was used to investigate the effects of Tet2-deficiency on neutrophils. Motility and phagocytosis were assessed through a Staphylococcus aureus phagocytosis assay. RNA sequencing (RNA-seq) was performed to analyze transcriptomic differences in Tet2-deficient neutrophils at baseline and after stimulation with S. aureus-derived lipoteichoic acid (LTA). DESeq2 and g:Profiler were used for differential expression analysis and functional annotation, respectively. Results: CHIP subjects had increased serum protein titers of MPO (p=0.006) and LTF (p=0.001) compared to controls, but MPO and LTF mRNA expression did not differ significantly. Tet2-deficient murine neutrophils exhibited impaired phagocytosis (p=0.034) and motility (p=0.004). Genes related to motility, the interferon response, and neutrophil development were dysregulated in Te…
abstract: Background: Clonal hematopoiesis of indeterminate potential (CHIP), a potential precursor to myelodysplastic syndrome (MDS), affects over 10% of adults over 65. Loss-of-function ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) variants are common in CHIP and associate with epigenetic dysregulation, inflammation, and cardiovascular disease. Although neutrophils are sensitive to epigenetic dysregulation and contribute to many cardiovascular diseases, the effects of TET2-deficiency on neutrophils have not been characterized. We hypothesize that TET2-deficiency dysregulates gene expression and function in neutrophils. Methods: With informed consent and ethics approval, serum and peripheral blood (PB) were collected from CHIP subjects and controls. RNA was extracted from whole PB and mRNA expression of two representative neutrophil granule genes, myeloperoxidase (MPO) and lactotransferrin (LTF), were assessed using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). MPO and LTF serum protein titers were quantified with enzyme-linked immunosorbent assays (ELISA). Additionally, the Tet2flox/flox Vav-iCre mouse model was used to investigate the effects of Tet2-deficiency on neutrophils. Motility and phagocytosis were assessed through a Staphylococcus aureus phagocytosis assay. RNA sequencing (RNA-seq) was performed to analyze transcriptomic differences in Tet2-deficient neutrophils at baseline and after stimulation with S. aureus-derived lipoteichoic acid (LTA). DESeq2 and g:Profiler were used for differential expression analysis and functional annotation, respectively. Results: CHIP subjects had increased serum protein titers of MPO (p=0.006) and LTF (p=0.001) compared to controls, but MPO and LTF mRNA expression did not differ significantly. Tet2-deficient murine neutrophils exhibited impaired phagocytosis (p=0.034) and motility (p=0.004). Genes related to motility, the interferon response, and neutrophil development were dysregulated in Te…
author: Luo, Michael
language: eng
keywords: CHIP, Neutrophil, Hematopoiesis, Genetics, TET2, Epigenetics
date modified: 2026-07-27T20:35:41Z
provider: Queens University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queens University

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1974/28060