TNFAIP3 Plays a Role in Aging of the Hematopoietic System

Smith, Molly A.; Culver-Cochran, Ashley E.; Adelman, Emmalee R.; Rhyasen, Garrett W.; Ma, Averil; Figueroa, María E.; Starczynowski, Daniel T.

doi:10.3389/fimmu.2020.536442

Cited by 17 publications

(10 citation statements)

References 49 publications

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“…2 ). Heterozygous deletion of A20 in young HSCs results in characteristic features of hematopoietic aging, including expansion of the HSC pool, reduced HSPC fitness, and myeloid-biased hematopoiesis due to increased NF-κB signaling ( Smith et al, 2020 ). Interestingly, a recent analysis identified frequent loss of one copy of TNFAIP3/A20 in aged healthy individuals with clonal hematopoiesis of Japanese descent ( Smith et al, 2020 ), and mutations in the myddosome adaptor MyD88 have been reported in previous studies of clonal hematopoiesis ( Genovese et al, 2014 ; Zink et al, 2017 ), linking innate immune dysregulation in aged HSCs and CHIP.…”

Section: Dysregulation Of Immune-related Pathways In Hematopoietic Premalignanciesmentioning

confidence: 99%

Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS

Trowbridge

Starczynowski

2021

Journal of Experimental Medicine

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126

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With a growing aged population, there is an imminent need to develop new therapeutic strategies to ameliorate disorders of hematopoietic aging, including clonal hematopoiesis and myelodysplastic syndrome (MDS). Cell-intrinsic dysregulation of innate immune- and inflammatory-related pathways as well as systemic inflammation have been implicated in hematopoietic defects associated with aging, clonal hematopoiesis, and MDS. Here, we review and discuss the role of dysregulated innate immune and inflammatory signaling that contribute to the competitive advantage and clonal dominance of preleukemic and MDS-derived hematopoietic cells. We also propose how emerging concepts will further reveal critical biology and novel therapeutic opportunities.

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Section: Dysregulation Of Immune-related Pathways In Hematopoietic Premalignanciesmentioning

confidence: 99%

Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS

Trowbridge

Starczynowski

2021

Journal of Experimental Medicine

Self Cite

126

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“…To achieve this, we first identified genes specifically affected in THP-1, but not in CD34 + cells. We identified all differentially expressed genes (DEGs) between THP-1 and CD34 + cells using publicly available transcriptome profiles (GSM2797289 and GSM2599707, respectively) ( Douglas et al, 2017 ; Smith et al, 2020 ). Quality control showed that all samples had sufficient sequencing depth and high per base quality ( Supplementary Figure S1 ).…”

Section: Resultsmentioning

confidence: 99%

RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation

Liu

Yang

Sun

et al. 2021

Front. Mol. Biosci.

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RUNX1 is a Runt family transcription factor that plays a critical role in normal hematopoiesis, including the differentiation and proliferation of hematopoietic cells. RUNX1 mutations, including chromosomal translocations, cause abnormal cell differentiation, but the mutation alone is not sufficient to cause leukemia. In MLL-fusion-induced leukemia, dysregulated wild-type RUNX1 can promote leukemia survival. Nevertheless, the underlying mechanisms of dysregulated wild-type RUNX1 in leukemia development have not been fully elucidated. This study overexpressed and knocked down RUNX1 expression in THP-1 human leukemia cells and CD34+ hematopoietic stem/progenitor cells to investigate the biological functions affected by dysregulated RUNX1. Our data indicated RUNX1 facilitated proliferation to promote leukemia cell growth. Furthermore, we demonstrated that RUNX1 knockdown in leukemia cells drastically diminished colony-forming ability. Finally, the RUNX1-knocked down cell depletion phenotype could be rescued by overexpression of CENPE, a cell proliferation gene and a RUNX1 direct target gene. Our results indicate a possible mechanism involving the RUNX1-CENPE axis on promoting leukemic cell growth.

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“…Furthermore, TNFAIP3 protects osteoprogenitors from undergoing apoptosis stimulated by TNF‐α 46 . More recently, this gene was found to maintain a young state in hematopoietic stem and progenitor cells (HSPC): namely, the expression level of TNFAIP3 was lower in aged HSPC than that in young HSPC, and partial deletion of TNFAIP3 in young HSPC results in typical features of aging 47 . Here, the expression of TNFAIP3 was promoted by dexamethasone, suggesting that it exerted immune‐regulating effect through activating TNFAIP3 .…”

Section: Discussionmentioning

confidence: 99%

Genome wide analysis of dexamethasone stimulated mineralization in human dental pulp cells by RNA sequencing

Tang

Wang

2022

The Journal of Gene Medicine

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Human dental pulp cells (hDPCs) contain mesenchymal stem cells and are therefore indispensible for reparative dentin formation. Here, we present a pilot study of transcriptomic profiles of mineralized hDPCs isolated from sound human maxillary third molars. We observed altered gene expression of hDPCs between control (dexamethasone free) and experimental (dexamethasone 1 nm) groups. Differential expression analysis revealed up‐regulation of several inflammation and mineralization‐related genes in the experimental group. After a Gene Ontology analysis for predicting genes involved in biological process, cellular component and molecular function, we found enrichment of genes related to protein binding. Based on the results of Kyoto Encylopedia of Genes and Genomes pathway analysis, it is suggested up‐regulated genes in mineralized hDPCs were mostly enriched in the mitogen‐activated protein kinase (MAPK) signaling pathway, fluid shear stress and the atherosclerosis signaling pathway, etc. Importantly, Gene Set Enrichment Analysis revealed dexamethasone was positively related to the Janus kinase/signal transducer and activator of transcription, MAPK and Notch signaling pathway. Moreover, it was suggested that dexamethasone regulates signaling pathway in pluripotency of stem cells. Collectively, our work highlights transcriptome level gene regulation and intercellular interactions in mineralized hDPCs. The database produced in the present study paves the way for further investigations looking to explore genes that are involved in dental pulp cells mineralization.

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TNFAIP3 Plays a Role in Aging of the Hematopoietic System

Cited by 17 publications

References 49 publications

Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS

Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS

RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation

Genome wide analysis of dexamethasone stimulated mineralization in human dental pulp cells by RNA sequencing

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