Bone Marrow Stroma-Induced Transcriptome and Regulome Signatures of Multiple Myeloma

Dziadowicz, Sebastian A.; Wang, Lei; Akhter, Halima; Aesoph, Drake; Sharma, Teenu; Adjeroh, Donald A.; Hazlehurst, Lori A.; Hu, Gangqing

doi:10.3390/cancers14040927

Cited by 17 publications

(19 citation statements)

References 99 publications

(189 reference statements)

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“…NextSeq2000 was used to generate the sequencing data of 36 million clusters (or 72 million F + R reads) per sample with the P3 flow cell at Marshal University Genomics Core (Huntington, WV, USA). RNA-Seq data analysis follows our previous work [ 34 , 35 ]: briefly, RNA-Seq read aligned to human genome by subread [ 36 ], read counts summarized based on RefSeq gene annotation by featurecount [ 37 ], expression level quantification by RPKM [ 38 ] with an in-house script, visualization of gene expression by MeV [ 39 ], prediction of differentially expressed (DE) genes by EdgeR (FDR = 0.05; |log2FC| > 1, and log2(Count Per million) > 0), and gene set enrichment analysis against hallmark gene sets by GSEA [ 40 , 41 ].…”

Section: Methodsmentioning

confidence: 99%

Redox imbalance in COVID-19 pathophysiology

Majumder¹,

Deepak²,

Hadique³

et al. 2022

Redox Biology

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Section: Methodsmentioning

confidence: 99%

Redox imbalance in COVID-19 pathophysiology

Majumder¹,

Deepak²,

Hadique³

et al. 2022

Redox Biology

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“…RNA-Seq data processing followed our previous procedures ( 56 , 57 ). In brief, single end RNA-Seq reads were aligned to the mouse reference genome (mm10) by sub-read ( 58 ).…”

Section: Methodsmentioning

confidence: 99%

Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice

et al. 2023

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In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces monocyte differentiation into a heterogenous population of monocyte-derived dendritic cells (moDCs) and macrophages. However, the downstream molecular signals that dictate the differentiation of monocytes under pathological conditions is incompletely understood. We report here that the GM-CSF-induced STAT5 tetramerization is a critical determinate of monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs. Conversely, the absence of STAT5 tetramers results in a switch to a functionally distinct monocyte-derived macrophage population. In the dextran sulfate sodium (DSS) model of colitis, STAT5 tetramer-deficient monocytes exacerbate disease severity. Mechanistically, GM-CSF signaling in STAT5 tetramer-deficient monocytes results in the overexpression of arginase I and a reduction in nitric oxide synthesis following stimulation with lipopolysaccharide. Correspondingly, the inhibition of arginase I activity and sustained supplementation of nitric oxide ameliorates the worsened colitis in STAT5 tetramer-deficient mice. This study suggests that STAT5 tetramers protect against severe intestinal inflammation through the regulation of arginine metabolism.

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“…RNA-Seq data analysis followed our previous work ( 24 ). Pair-end RNA-Seq read were mapped to the mouse genome (mm10) by subread v2.0.1 with default parameters ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

Interleukin-27-dependent transcriptome signatures during neonatal sepsis

et al. 2023

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Human newborns exhibit increased vulnerability and risk of mortality from infection that is consistent with key differences in the innate and adaptive immune responses relative to those in adult cells. We have previously shown an increase in the immune suppressive cytokine, IL-27, in neonatal cells and tissues from mice and humans. In a murine model of neonatal sepsis, mice deficient in IL-27 signaling exhibit reduced mortality, increased weight gain, and better control of bacteria with reduced systemic inflammation. To explore a reprogramming of the host response in the absence of IL-27 signaling, we profiled the transcriptome of the neonatal spleen during Escherichia coli-induced sepsis in wild-type (WT) and IL-27Rα-deficient (KO) mice. We identified 634 genes that were differentially expressed, and those most upregulated in WT mice were associated with inflammation, cytokine signaling, and G protein coupled receptor ligand binding and signaling. These genes failed to increase in the IL-27Rα KO mice. We further isolated an innate myeloid population enriched in macrophages from the spleens of control and infected WT neonates and observed similar changes in gene expression aligned with changes in chromatin accessibility. This supports macrophages as an innate myeloid population contributing to the inflammatory profile in septic WT pups. Collectively, our findings highlight the first report of improved pathogen clearance amidst a less inflammatory environment in IL-27Rα KO. This suggests a direct relationship between IL-27 signaling and bacterial killing. An improved response to infection that is not reliant upon heightened levels of inflammation offers new promise to the potential of antagonizing IL-27 as a host-directed therapy for neonates.

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Bone Marrow Stroma-Induced Transcriptome and Regulome Signatures of Multiple Myeloma

Cited by 17 publications

References 99 publications

Redox imbalance in COVID-19 pathophysiology

Redox imbalance in COVID-19 pathophysiology

Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice

Interleukin-27-dependent transcriptome signatures during neonatal sepsis

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