The transcriptional regulation of normal and malignant blood cell development

Edginton-White, Benjamin; Bonifer, Constanze

doi:10.1111/febs.15735

Cited by 27 publications

(19 citation statements)

References 146 publications

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“…The review by Benjamin Edginton‐White and Constanze Bonifer [9] also included in this issue focuses on the transcriptional and epigenetic regulators involved in blood cell development. Here, the authors highlight how the complex process of blood cell differentiation is coordinated by the crosstalk between transcription factors and chromatin architecture regulators.…”

Section: Aberrant Epigenetic Profiles In Cancermentioning

confidence: 99%

Cancer epigenetics: promises and pitfalls for cancer therapy

Skourti¹,

Dhillon²

2022

The FEBS Journal

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Over the past few decades, epigenetic regulators have emerged as major players in cellular processes that drive cancer initiation and progression, and subsequently modulate the responsiveness of cancers to therapeutic agents. This Special Issue of The FEBS Journal, Cancer Epigenetics, features an exciting collection of review articles that focus on the functions of a broad spectrum of epigenetic modulators in cancer. The diverse topics explored herein range from the roles of transposable elements and chromatin architecture in cancer and the most recent research advances on cancer‐associated histone variants (oncohistones), to the effects of altered epigenetics on transcription and advanced cancer cell phenotypes. Moreover, the prospective key function of cancer metabolism in linking epigenetics and transcriptional regulation, and the potential of epigenetics for targeted cancer therapeutics is discussed. We hope that this collection of articles will give readers an enlightening overview of the most recent advances in the fast‐moving field of cancer epigenetics.

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Section: Aberrant Epigenetic Profiles In Cancermentioning

confidence: 99%

Cancer epigenetics: promises and pitfalls for cancer therapy

Skourti¹,

Dhillon²

2022

The FEBS Journal

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“…In the bone marrow (BM), HSCs reside in a very specialized environment, called the hematopoietic stem cell niche [3][4][5]. There, an array of intrinsic and extrinsic signaling pathways and multiple transcription factors (TFs) regulate HSPC maintenance [6][7][8]. HSPCs are identified as Lin − Sca1 + c-Kit + (LSK) cells, which are lineage marker negative and express both the stem cell antigen-1 (Sca1) and stem cell factor receptor (c-Kit/CD117).…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic Stem and Progenitor Cell Maintenance and Multiple Lineage Differentiation Is an Integral Function of NFATc1

Brito

Klein-Heßling

Serfling

et al. 2022

Cells

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Hematopoietic stem and progenitor cell (HSPC) maintenance and the differentiation of various lineages is a highly complex but precisely regulated process. Multiple signaling pathways and an array of transcription factors influence HSPC maintenance and the differentiation of individual lineages to constitute a functional hematopoietic system. Nuclear factor of activated T cell (NFAT) family transcription factors have been studied in the context of development and function of multiple mature hematopoietic lineage cells. However, until now their contribution in HSPC physiology and HSPC differentiation to multiple hematopoietic lineages has remained poorly understood. Here, we show that NFAT proteins, specifically NFATc1, play an indispensable role in the maintenance of HSPCs. In the absence of NFATc1, very few HSPCs develop in the bone marrow, which are functionally defective. In addition to HSPC maintenance, NFATc1 also critically regulates differentiation of lymphoid, myeloid, and erythroid lineage cells from HSPCs. Deficiency of NFATc1 strongly impaired, while enhanced NFATc1 activity augmented, the differentiation of these lineages, which further attested to the vital involvement of NFATc1 in regulating hematopoiesis. Hematopoietic defects due to lack of NFATc1 activity can lead to severe pathologies such as lymphopenia, myelopenia, and a drastically reduced lifespan underlining the critical role NFATc1 plays in HSPC maintenance and in the differentaion of various lineages. Our findings suggest that NFATc1 is a critical component of the myriad signaling and transcriptional regulators that are essential to maintain normal hematopoiesis.

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“…With an abundance of binding sites for miRNA and mRNA, lncRNA can act as ceRNA (competing endogenous RNA) and are significant regulatory elements in post-transcriptional gene expression (Carpenter et al, 2014; Wissink et al, 2016), while TFs are proteins capable of altering or activating gene-expression level (Boija et al, 2018; Edginton-White and Bonifer, 2022; Mitsis et al, 2020; Sharov et al, 2022). Multiple miRNA databases such as miRWalk (Sticht et al, 2018), miRNet (Chang et al, 2020), and TargetScan (Agarwal et al, 2015) compute potential miRNA-mRNA interactions, while the role of individual miRNA can be inferred through functional analysis with Gene Ontology (GO) (Carbon et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analyses of differentially expressed genes, micro RNAs and long-non-coding RNAs in severe, symptomatic and asymptomatic malaria infection

Oboh

Morenikeji

Ojurongbe

et al. 2022

Preprint

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Background: Malaria transmission and endemicity in Africa remains hugely disproportionate compared to the rest of the world. The complex life cycle of P. falciparum (Pf) between the vertebrate human host and the anopheline vector results in differential expression of genes within and between hosts. An in-depth understanding of Pf interaction with various human genes through regulatory elements will pave way for identification of additional tool in the arsenal for malaria control. Therefore, the regulatory elements (REs) involved in the over- or under-expression of various host immune genes hold a key to alternative control measures that can be applied for prompt diagnosis and treatment. Methods: We carried out an RNAseq analysis to identify differentially expressed genes and network analysis of non-coding RNAs and target genes associated with immune response in individuals with different clinical outcomes. Raw RNAseq datasets, retrieved for analyses include individuals with severe (Gambia - 20), symptomatic (Burkina Faso - 15), asymptomatic (Mali - 16) malaria as well as uninfected controls (Tanzania - 20; Mali - 36). Results: Of the total 107 datasets retrieved, we identified 5534 differentially expressed genes (DEGs) among disease and control groups. A peculiar pattern of DEGs was observed, with individuals presenting with severe/symptomatic malaria having the highest and most diverse upregulated genes, while a reverse phenomenon was recorded among the asymptomatic and uninfected individuals. In addition, we identified 141 differentially expressed (DE) miRNA, of which 78 and 63 were upregulated and downregulated respectively. Interactome analysis revealed a moderate interaction between DEGs and miRNAs. Of all identified miRNA, five were unique (hsa-mir-32, hsa-mir-25, hsa-mir-221, hsa-mir-29 and hsa-mir-148) because of their connectivity to several genes, including hsa-mir-221 connected to 16 genes. Six-hundred and eight DE lncRNA were identified, including SLC7A11, LINC01524 among the upregulated ones. Conclusion: Our study provides important insights into host immune genes undergoing differential expression under different malaria conditions. It also identified unique miRNAs and lncRNAs that modify and/or regulate the expression of various immune genes. These regulatory elements, we surmise have the potential to serve a diagnostic purpose in discriminating between individuals with severe/symptomatic malaria and those with asymptomatic infection or uninfected.

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The transcriptional regulation of normal and malignant blood cell development

Cited by 27 publications

References 146 publications

Cancer epigenetics: promises and pitfalls for cancer therapy

Cancer epigenetics: promises and pitfalls for cancer therapy

Hematopoietic Stem and Progenitor Cell Maintenance and Multiple Lineage Differentiation Is an Integral Function of NFATc1

Transcriptomic analyses of differentially expressed genes, micro RNAs and long-non-coding RNAs in severe, symptomatic and asymptomatic malaria infection

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