Toward a Reference Gene Catalog of Human Primary Monocytes

Mirsafian, Hoda; Ripen, Adiratna Mat; Manaharan, Thamilvaani; Mohamad, Saharuddin Bin; Merican, Amir Feisal

doi:10.1089/omi.2016.0124

Cited by 11 publications

(8 citation statements)

References 42 publications

(35 reference statements)

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“…Recent transcriptomic analyses provide effective characterization of the expression of potential key regulatory genes in subsets of human monocytes. 10 Evaluation of cell proliferation-related signaling pathways have shown the enhanced sensitivity of CMML monocytes and other cells to granulocyte-macrophage-CSF. Classical and intermediate monocytes are recruited into different tissues through the chemokine C-C receptor 2, whereas this occurs via the chemokine CX3C receptor 1 for nonclassical monocytes.…”

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confidence: 99%

The classical nature of distinctive CMML monocytes

Greenberg¹

2017

Blood

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procoagulant proteins which, along with the disrupted and activated surface of cell membrane of the cell from which they arise, form a template for coagulation and fibrinolysis.7 The cell-free DNA (cf-DNA)released by the formation of NETs can also activate coagulation via the contact activation system. figure). Through a series of experiments, the authors demonstrate the presence of ETosis in malignant promyelocytes and the effect of ATRA in potentiating and inducing extracellular chromatin release in a timedependent manner. They demonstrate that this effect was prominent in the first 3 days after exposure to ATRA and, beyond that time period, cell death was predominantly due to conventional apoptosis. They further correlated thrombin generation and a strong procoagulant effect to extracellular chromatin and cf-DNA generated by ETosis and the ability of DNAse1 to decrease thrombin generation by degrading cf-DNA. The use of anti-tissue factor antibodies could not reverse this. Additional experiments demonstrated the ability of promyelocytic extracellular chromatin to induce fibrin deposition, plasmin generation, and fibrinolysis. Paradoxically, it impaired clot lysis. Finally, the authors demonstrate the cytotoxic effect of promyelocytic extracellular chromatin on the endothelial cells that they come in contact with. This cytotoxic effect converts these endothelial cells to a procoagulant phenotype, provides additional surface area on which coagulation and fibrin deposition can happen, and may also contribute to loss of integrity of the endothelium. Through the data in their paper, Cao et al demonstrate a novel mechanism of perturbation in coagulation and fibrinolysis in APL that is exacerbated on initiation of treatment with ATRA. The data suggest that targeting this novel mechanism could potentially address the problem of early coagulopathy-related mortality. The cytotoxic effects of promyelocytic extracellular chromatin on endothelial cells could also potentially explain the differentiation syndrome seen after initiation of therapy and apparent susceptibility to bleeding in the presence of what would otherwise be considered adequate hemostatic levels of platelets and coagulation factors.Conflict-of-interest disclosure: The author declares no competing financial interests. n

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confidence: 99%

The classical nature of distinctive CMML monocytes

Greenberg¹

2017

Blood

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“…), Colorectal cancer (?) EEF1A1P3 70 , 76 EEF1A1 pseudogene 3 13 13q12.2 1623 – EEF1A1P4 70 EEF1A1 pseudogene 4 12 12p12.3 1659 – EEF1A1P5 70 , 77 , 78 , 79 , 80 , 81 EEF1A1 pseudogene 5 9 9q34.13 1747 Hepatocellular carcinoma (? ), nasopharyngeal carcinoma (?…”

Section: Methodsmentioning

confidence: 99%

“…The EEF1A1 pseudogene 6, alias EEF1A1P6 , was first reported in 1996 70 and is highly expressed in human primary monocytes. 78 Subsequently, it is reported in a study on schizophrenia, 84 hepatocellular carcinoma, 31 multiple myeloma, 85 and in a dataset on rectum cancer. The contribution of EEF1A1P6 in these diseases is unknown.…”

Section: Methodsmentioning

confidence: 99%

The pseudogenes of eukaryotic translation elongation factors (EEFs): Role in cancer and other human diseases

Cristiano¹

2022

Genes & Diseases

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“…In addition, the molecular mechanisms underlying the functions of lncRNAs in primary monocytes of XLA have not been studied yet. We recently published a gene reference catalogue and lncRNAs landscape of human primary monocytes from healthy subjects 23, 24 . In this study, we performed deep high-throughput RNA sequencing (RNA-Seq) analysis on primary monocytes from XLA patients and healthy subjects to investigate the effect of BTK gene expression deficiency on innate immune function of XLA patients.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome profiling of monocytes from XLA patients revealed the innate immune function dysregulation due to the BTK gene expression deficiency

Mirsafian

Ripen

Leong

et al. 2017

Sci Rep

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X-linked agammaglobulinemia (XLA) is a rare genetic disorder, caused by mutations in BTK (Bruton’s Tyrosine Kinase) gene. Deep high-throughput RNA sequencing (RNA-Seq) approach was utilized to explore the possible differences in transcriptome profiles of primary monocytes in XLA patients compared with healthy subjects. Our analysis revealed the differences in expression of 1,827 protein-coding genes, 95 annotated long non-coding RNAs (lncRNAs) and 20 novel lincRNAs between XLA patients and healthy subjects. GO and KEGG pathway analysis of differentially expressed (DE) protein-coding genes showed downregulation of several innate immune-related genes and upregulation of oxidative phosphorylation and apoptosis-related genes in XLA patients compared to the healthy subjects. Moreover, the functional prediction analysis of DE lncRNAs revealed their potential role in regulating the monocytes cell cycle and apoptosis in XLA patients. Our results suggested that BTK mutations may contribute to the dysregulation of innate immune system and increase susceptibility to apoptosis in monocytes of XLA patients. This study provides significant finding on the regulation of BTK gene in monocytes and the potential for development of innovative biomarkers and therapeutic monitoring strategies to increase the quality of life in XLA patients.

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Toward a Reference Gene Catalog of Human Primary Monocytes

Cited by 11 publications

References 42 publications

The classical nature of distinctive CMML monocytes

The classical nature of distinctive CMML monocytes

The pseudogenes of eukaryotic translation elongation factors (EEFs): Role in cancer and other human diseases

Transcriptome profiling of monocytes from XLA patients revealed the innate immune function dysregulation due to the BTK gene expression deficiency

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