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Advances in the Epigenetic Regulation of Stem Cells in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 4478

Special Issue Editors


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Guest Editor
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
Interests: cell morphology; cell biology; ultrastructure; transmission electron microscopy; scanning electron microscopy; developmental biology

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Guest Editor
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
Interests: stem cell biology; cell differentiation; cellular mechanisms; cell senescence; stress response; gene and protein expression
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Special Issue Information

Dear Colleagues, 

Stem cells have peculiar properties, such as differentiation and self-renewal, which can be strongly influenced by epigenetic changes and environmental stressors. Molecular biology and cell morphology studies, through fluorescence and electron microscopy methods, have allowed for the highlighting of alterations, at the mitochondrial level, associated with several diseases. Unraveling epigenetic factors and their roles in influencing pluripotency as well as stem cell differentiation capabilities could pave the way for new therapeutic approaches in regenerative medicine. This Special Issue will include a selection of research papers and reviews concerning various aspects of the molecular and epigenetic regulation of stem cell behavior. In addition, clinical studies evaluating epigenetics and stem cells in regenerative medicine are suitable to be submitted to this Special Issue.

Dr. Pasquale Bandiera
Dr. Sara Cruciani
Guest Editors

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Keywords

  • stem cells
  • cell differentiation
  • epigenetic mechanism
  • cell morphology
  • regenerative medicine

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Published Papers (3 papers)

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Research

15 pages, 2428 KiB  
Article
Effects of the MCF-7 Exhausted Medium on hADSC Behaviour
by Giuseppe Garroni, Sara Cruciani, Diletta Serra, Renzo Pala, Donatella Coradduzza, Maria Laura Cossu, Giorgio Carlo Ginesu, Carlo Ventura and Margherita Maioli
Int. J. Mol. Sci. 2024, 25(13), 7026; https://doi.org/10.3390/ijms25137026 - 27 Jun 2024
Viewed by 674
Abstract
Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are [...] Read more.
Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are privileged candidates for regenerative medicine procedures or other plastic reconstructive surgeries. The cellular environment is able to influence the fate of stem cells residing in the tissue. In a previous study, we exposed hADSCs to an exhausted medium of a breast cancer cell line (MCF-7) recovered at different days (4, 7, and 10 days). In the same paper, we inferred that the medium was able to influence the behaviour of stem cells. Considering these results, in the present study, we evaluated the expression of the major genes related to adipogenic and osteogenic differentiation. To confirm the gene expression data, oil red and alizarin red colorimetric assays were performed. Lastly, we evaluated the expression of miRNAs influencing the differentiation process and the proliferation rate, maintaining a proliferative state. The data obtained confirmed that cells exposed to the medium maintained a stem and proliferative state that could lead to a risky proliferative phenotype. Full article
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15 pages, 2756 KiB  
Article
Epigenetic and Transcriptional Shifts in Human Neural Stem Cells after Reprogramming into Induced Pluripotent Stem Cells and Subsequent Redifferentiation
by Carolin Haubenreich, Michael Lenz, Andreas Schuppert, Michael Peitz, Philipp Koch, Martin Zenke and Oliver Brüstle
Int. J. Mol. Sci. 2024, 25(6), 3214; https://doi.org/10.3390/ijms25063214 - 12 Mar 2024
Viewed by 1344
Abstract
Induced pluripotent stem cells (iPSCs) and their derivatives have been described to display epigenetic memory of their founder cells, as well as de novo reprogramming-associated alterations. In order to selectively explore changes due to the reprogramming process and not to heterologous somatic memory, [...] Read more.
Induced pluripotent stem cells (iPSCs) and their derivatives have been described to display epigenetic memory of their founder cells, as well as de novo reprogramming-associated alterations. In order to selectively explore changes due to the reprogramming process and not to heterologous somatic memory, we devised a circular reprogramming approach where somatic stem cells are used to generate iPSCs, which are subsequently re-differentiated into their original fate. As somatic founder cells, we employed human embryonic stem cell-derived neural stem cells (NSCs) and compared them to iPSC-derived NSCs derived thereof. Global transcription profiling of this isogenic circular system revealed remarkably similar transcriptomes of both NSC populations, with the exception of 36 transcripts. Amongst these we detected a disproportionately large fraction of X chromosomal genes, all of which were upregulated in iPSC-NSCs. Concurrently, we detected differential methylation of X chromosomal sites spatially coinciding with regions harboring differentially expressed genes. While our data point to a pronounced overall reinstallation of autosomal transcriptomic and methylation signatures when a defined somatic lineage is propagated through pluripotency, they also indicate that X chromosomal genes may partially escape this reinstallation process. Considering the broad application of iPSCs in disease modeling and regenerative approaches, such reprogramming-associated alterations in X chromosomal gene expression and DNA methylation deserve particular attention. Full article
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13 pages, 8418 KiB  
Article
Embryonic Stem Cells Can Generate Oral Epithelia under Matrix Instruction
by Ridhima Das, Lisa Harper, Kayoko Kitajima, Tarig Al-Hadi Osman, Mihaela Roxana Cimpan, Anne Chr. Johannssen, Salwa Suliman, Ian C. Mackenzie and Daniela-Elena Costea
Int. J. Mol. Sci. 2023, 24(9), 7694; https://doi.org/10.3390/ijms24097694 - 22 Apr 2023
Cited by 1 | Viewed by 1736
Abstract
We aimed to investigate whether molecular clues from the extracellular matrix (ECM) can induce oral epithelial differentiation of pluripotent stem cells. Mouse embryonic stem cells (ESC) of the feeder-independent cell line E14 were used as a model for pluripotent stem cells. They were [...] Read more.
We aimed to investigate whether molecular clues from the extracellular matrix (ECM) can induce oral epithelial differentiation of pluripotent stem cells. Mouse embryonic stem cells (ESC) of the feeder-independent cell line E14 were used as a model for pluripotent stem cells. They were first grown in 2D on various matrices in media containing vitamin C and without leukemia inhibitory factor (LIF). Matrices investigated were gelatin, laminin, and extracellular matrices (ECM) synthesized by primary normal oral fibroblasts and keratinocytes in culture. Differentiation into epithelial lineages was assessed by light microscopy, immunocytochemistry, and flow cytometry for cytokeratins and stem cell markers. ESC grown in 2D on various matrices were afterwards grown in 3D organotypic cultures with or without oral fibroblasts in the collagen matrix and examined histologically and by immunohistochemistry for epithelial (keratin pairs 1/10 and 4/13 to distinguish epidermal from oral epithelia and keratins 8,18,19 to phenotype simple epithelia) and mesenchymal (vimentin) phenotypes. ECM synthesized by either oral fibroblasts or keratinocytes was able to induce, in 2D cultures, the expression of cytokeratins of the stratified epithelial phenotype. When grown in 3D, all ESC developed into two morphologically distinct cell populations on collagen gels: (i) epithelial-like cells organized in islands with occasional cyst- or duct-like structures and (ii) spindle-shaped cells suggestive of mesenchymal differentiation. The 3D culture on oral fibroblast-populated collagen matrices was necessary for further differentiation into oral epithelia. Only ESC initially grown on 2D keratinocyte or fibroblast-synthesized matrices reached full epithelial maturation. In conclusion, ESC can generate oral epithelia under matrix instruction. Full article
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