Molecular mechanisms of reprogramming of differentiated cells into stem cells in the moss Physcomitrium patens

Neovascularization and angiogenesis are vital processes in the repair of damaged tissue, creating new blood vessel networks and increasing oxygen and nutrient supply for regeneration. The importance of Adipose-derived Mesenchymal Stem Cells (ASCs) contained in the adipose tissue surrounding blood vessel networks to these processes remains unknown and the exact mechanisms responsible for directing adipogenic cell fate remain to be discovered. As adipose tissue contains a heterogenous population of partially differentiated cells of adipocyte lineage; tissue repair, angiogenesis and neovascularization may be closely linked to the function of ASCs in a complex relationship. This review aims to investigate the link between ASCs and angiogenesis/neovascularization, with references to current studies. The molecular mechanisms of these processes, as well as ASC differentiation and proliferation are described in detail. ASCs may differentiate into endothelial cells during neovascularization; however, recent clinical trials have suggested that ASCs may also stimulate angiogenesis and neovascularization indirectly through the release of paracrine factors.

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Regulation of CXCR6 Expression on Adipocytes and Osteoblasts Differentiated from Human Adipose Tissue-Derived Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2020/8870133 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Seung-Cheol Lee ◽

Yoo-Jung Lee ◽

Min Kyoung Shin ◽

Jung-Suk Sung

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Cell Activation ◽

Molecular Mechanisms ◽

De Novo ◽

Human Mesenchymal Stem Cells ◽

De Novo Synthesis ◽

Differentiation Potential ◽

Differentiated Cells

Human mesenchymal stem cells derived from adipose tissue (hADMSCs) are a desirable candidate in regenerative medicine. hADMSCs secrete growth factors, cytokines, and chemokines and also express various receptors that are important in cell activation, differentiation, and migration to injured tissue. We showed that the expression level of chemokine receptor CXCR6 was significantly increased by ~2.5-fold in adipogenic-differentiated cells (Ad), but not in osteogenic-differentiated cells (Os) when compared with hADMSCs. However, regulation of CXCR6 expression on hADMSCs by using lentiviral particles did not affect the differentiation potential of hADMSCs. Increased expression of CXCR6 on Ad was mediated by both receptor recycling, which was in turn regulated by secretion of CXCL16, and de novo synthesis. The level of soluble CXCL16 was highly increased in both Ad and Os in particular, which inversely correlates with the expression on a transmembrane-bound form of CXCL16 that is cleaved by disintegrin and metalloproteinase. We concluded that the expression of CXCR6 is regulated by receptor degradation or recycling when it is internalized by interaction with CXCL16 and by de novo synthesis of CXCR6. Overall, our study may provide an insight into the molecular mechanisms of the CXCR6 reciprocally expressed on differentiated cells from hADMSCs.

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Muscle stem cell and physical activity: what point is the debate at?

Open Medicine ◽

10.1515/med-2017-0022 ◽

2017 ◽

Vol 12 (1) ◽

pp. 144-156 ◽

Cited By ~ 4

Author(s):

Gabriele Ceccarelli ◽

Laura Benedetti ◽

Maria Luisa Arcari ◽

Cecilia Carubbi ◽

Daniela Galli

Keyword(s):

Physical Activity ◽

Stem Cells ◽

Physical Exercise ◽

Cardiac Muscle ◽

Weight Control ◽

Molecular Mechanisms ◽

Post Injury ◽

Muscle Stem Cells ◽

Positive Effects ◽

Differentiated Cells

AbstractIn the last 15 years, it emerged that the practice of regular physical activity reduces the risks of many diseases (cardiovascular diseases, diabetes, etc.) and it is fundamental in weight control and energy consuming to contrast obesity. Different groups proposed many molecular mechanisms as responsible for the positive effects of physical activity in healthy life. However, many points remain to be clarified. In this mini-review we reported the latest observations on the effects of physical exercise on healthy skeletal and cardiac muscle focusing on muscle stem cells. The last ones represent the fundamental elements for muscle regeneration post injury, but also for healthy muscle homeostasis.Interestingly, in both muscle tissues the morphological consequence of physical activity is a physiological hypertrophy that depends on different phenomena both in differentiated cells and stem cells. The signaling pathways for physical exercise effects present common elements in skeletal and cardiac muscle, like activation of specific transcription factors, proliferative pathways, and cytokines. More recently, post translational (miRNAs) or epigenetic (DNA methylation) modifications have been demonstrated. However, several points remain unresolved thus requiring new research on the effect of exercise on muscle stem cells.

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iPSC Preparation and Epigenetic Memory: Does the Tissue Origin Matter?

Cells ◽

10.3390/cells10061470 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1470

Author(s):

Giuseppe Scesa ◽

Raffaella Adami ◽

Daniele Bottai

Keyword(s):

Stem Cells ◽

Molecular Mechanisms ◽

Embryonic Stem ◽

Epigenetic Memory ◽

Differentiated Cells ◽

Ipsc Generation ◽

Tissue Of Origin ◽

Induced Pluripotent ◽

The Impact

The production of induced pluripotent stem cells (iPSCs) represent a breakthrough in regenerative medicine, providing new opportunities for understanding basic molecular mechanisms of human development and molecular aspects of degenerative diseases. In contrast to human embryonic stem cells (ESCs), iPSCs do not raise any ethical concerns regarding the onset of human personhood. Still, they present some technical issues related to immune rejection after transplantation and potential tumorigenicity, indicating that more steps forward must be completed to use iPSCs as a viable tool for in vivo tissue regeneration. On the other hand, cell source origin may be pivotal to iPSC generation since residual epigenetic memory could influence the iPSC phenotype and transplantation outcome. In this paper, we first review the impact of reprogramming methods and the choice of the tissue of origin on the epigenetic memory of the iPSCs or their differentiated cells. Next, we describe the importance of induction methods to determine the reprogramming efficiency and avoid integration in the host genome that could alter gene expression. Finally, we compare the significance of the tissue of origin and the inter-individual genetic variation modification that has been lightly evaluated so far, but which significantly impacts reprogramming.

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Transcription Factors, R-Loops and Deubiquitinating Enzymes: Emerging Targets in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers13153753 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3753

Author(s):

Silvia M. L. Barabino ◽

Elisabetta Citterio ◽

Antonella Ellena Ronchi

Keyword(s):

Stem Cells ◽

Transcription Factors ◽

Rna Splicing ◽

Molecular Mechanisms ◽

Driver Mutations ◽

Deubiquitinating Enzymes ◽

Hematopoietic Stem ◽

Cellular Processes ◽

Differentiated Cells ◽

Dna Damage Signaling

Myeloid neoplasms encompass a very heterogeneous family of diseases characterized by the failure of the molecular mechanisms that ensure a balanced equilibrium between hematopoietic stem cells (HSCs) self-renewal and the proper production of differentiated cells. The origin of the driver mutations leading to preleukemia can be traced back to HSC/progenitor cells. Many properties typical to normal HSCs are exploited by leukemic stem cells (LSCs) to their advantage, leading to the emergence of a clonal population that can eventually progress to leukemia with variable latency and evolution. In fact, different subclones might in turn develop from the original malignant clone through accumulation of additional mutations, increasing their competitive fitness. This process ultimately leads to a complex cancer architecture where a mosaic of cellular clones—each carrying a unique set of mutations—coexists. The repertoire of genes whose mutations contribute to the progression toward leukemogenesis is broad. It encompasses genes involved in different cellular processes, including transcriptional regulation, epigenetics (DNA and histones modifications), DNA damage signaling and repair, chromosome segregation and replication (cohesin complex), RNA splicing, and signal transduction. Among these many players, transcription factors, RNA splicing proteins, and deubiquitinating enzymes are emerging as potential targets for therapeutic intervention.

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Cross-Talk between Inflammatory Mediators and the Epithelial Mesenchymal Transition Process in the Development of Thyroid Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms20102466 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2466 ◽

Cited By ~ 4

Author(s):

Giovanna Revilla ◽

Rosa Corcoy ◽

Antonio Moral ◽

Joan Carles Escolà-Gil ◽

Eugenia Mato

Keyword(s):

Stem Cells ◽

Thyroid Gland ◽

Inflammatory Mediators ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Metabolic Reprogramming ◽

High Density Lipoproteins ◽

Mesenchymal Transition ◽

Differentiated Cells

There is strong association between inflammatory processes and their main metabolic mediators, such as leptin, adiponectin secretion, and low/high-density lipoproteins, with the cancer risk and aggressive behavior of solid tumors. In this scenario, cancer cells (CCs) and cancer stem cells (CSCs) have important roles. These cellular populations, which come from differentiated cells and progenitor stem cells, have increased metabolic requirements when it comes to maintaining or expanding the tumors, and they serve as links to some inflammatory mediators. Although the molecular mechanisms that are involved in these associations remain unclear, the two following cellular pathways have been suggested: 1) the mesenchymal-epithelial transition (MET) process, which permits the differentiation of adult stem cells throughout the acquisition of cell polarity and the adhesion to epithelia, as well to new cellular lineages (CSCs); and, 2) a reverse process, termed the epithelial-mesenchymal transition (EMT), where, in pathophysiological conditions (tissue injury, inflammatory process, and oxidative stress), the differentiated cells can acquire a multipotent stem cell-like phenotype. The molecular mechanisms that regulate both EMT and MET are complex and poorly understood. Especially, in the thyroid gland, little is known regarding MET/EMT and the role of CCs or CSCs, providing an exciting, new area of knowledge to be investigated. This article reviews the progress to date in research on the role of inflammatory mediators and metabolic reprogramming during the carcinogenesis process of the thyroid gland and the EMT pathways.

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Pathological LSD1 mutations cause HDAC-mediated aberrant gene repression during early cell differentiation

10.1101/2021.08.11.455900 ◽

2021 ◽

Author(s):

Daria Bunina ◽

Pierre-Luc Germain ◽

Alejandro Lopez Tobon ◽

Nadine Fernandez-Novel Marx ◽

Christian Arnold ◽

...

Keyword(s):

Stem Cells ◽

Protein Function ◽

Histone Deacetylases ◽

Molecular Mechanisms ◽

Target Genes ◽

De Novo ◽

Neurodevelopmental Disorder ◽

Differentiated Cells ◽

Lineage Differentiation ◽

Lysine Specific Demethylase

Lysine-specific demethylase 1 (LSD1/KDM1A) removes methylation of histone and non-histone substrates, and recruits a repressive chromatin complex. De novo LSD1 mutations impairing protein function lead to a rare neurodevelopmental disorder, but the molecular mechanisms of the pathology are unclear. Using patient-derived fibroblasts, reprogrammed pluripotent stem cells, and differentiated cells, we found over 4000 differentially expressed genes and 68 transcription factors (TFs) whose motif accessibilities changed upon LSD1 mutation. An enhancer-mediated gene regulatory network approach identified impaired transcriptional repressor activity in fibroblast and stem cells, leading to erroneous activation of their target genes. Furthermore, our analysis revealed overall decreases in TF target genes specifically during early lineage differentiation of LSD1 mutant stem cells, likely caused by increased activity of repressive co-factors of LSD1 - histone deacetylases (HDACs). Consistently, HDAC inhibitor restored changes in gene expression including downregulation phenotype. Our findings provide insights into pathogenesis of LSD1 mutations and targets for further therapeutic studies.

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Stem Cell Niches in Glioblastoma: A Neuropathological View

BioMed Research International ◽

10.1155/2014/725921 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

Davide Schiffer ◽

Marta Mellai ◽

Laura Annovazzi ◽

Valentina Caldera ◽

Angela Piazzi ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Stem Cell ◽

Tumor Cells ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Mechanisms Of Resistance ◽

Differentiated Cells ◽

Thin Ring ◽

Stem Cell Niches

Glioblastoma (GBM) stem cells (GSCs), responsible for tumor growth, recurrence, and resistance to therapies, are considered the real therapeutic target, if they had no molecular mechanisms of resistance, in comparison with the mass of more differentiated cells which are insensitive to therapies just because of being differentiated and nonproliferating. GSCs occur in tumor niches where both stemness status and angiogenesis are conditioned by the microenvironment. In both perivascular and perinecrotic niches, hypoxia plays a fundamental role. Fifteen glioblastomas have been studied by immunohistochemistry and immunofluorescence for stemness and differentiation antigens. It has been found that circumscribed necroses develop inside hyperproliferating areas that are characterized by high expression of stemness antigens. Necrosis developed inside them because of the imbalance between the proliferation of tumor cells and endothelial cells; it reduces the number of GSCs to a thin ring around the former hyperproliferating area. The perinecrotic GSCs are nothing else that the survivors remnants of those populating hyperproliferating areas. In the tumor, GSCs coincide with malignant areas so that the need to detect where they are located is not so urgent.

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Molecular Mechanisms Underlying the Functions of Cellular Markers Associated with the Phenotype of Cancer Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666180821154752 ◽

2019 ◽

Vol 14 (5) ◽

pp. 405-420 ◽

Cited By ~ 2

Author(s):

Eduardo Alvarado-Ortiz ◽

Miguel Á. Sarabia-Sánchez ◽

Alejandro García-Carrancá

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Molecular Mechanisms ◽

Tumor Biology ◽

Molecular Tools ◽

Recent Past ◽

Functional Roles ◽

Cellular Population ◽

Cellular Markers ◽

A Minor

Cancer Stem Cells (CSC) generally constitute a minor cellular population within tumors that exhibits some capacities of normal Stem Cells (SC). The existence of CSC, able to self-renew and differentiate, influences central aspects of tumor biology, in part because they can continue tumor growth, give rise to metastasis, and acquire drug and radioresistance, which open new avenues for therapeutics. It is well known that SC constantly interacts with their niche, which includes mesenchymal cells, extracellular ligands, and the Extra Cellular Matrix (ECM). These interactions regularly lead to homeostasis and maintenance of SC characteristics. However, the exact participation of each of these components for CSC maintenance is not clear, as they appear to be context- or cell-specific. In the recent past, surface cellular markers have been fundamental molecular tools for identifying CSC and distinguishing them from other tumor cells. Importantly, some of these cellular markers have been shown to possess functional roles that affect central aspects of CSC. Likewise, some of these markers can participate in regulating the interaction of CSC with their niche, particularly the ECM. We focused this review on the molecular mechanisms of surface cellular markers commonly employed to identify CSC, highlighting the signaling pathways and mechanisms involved in CSC-ECM interactions, through each of the cellular markers commonly used in the study of CSC, such as CD44, CD133, CD49f, CD24, CXCR4, and LGR5. Their presence does not necessarily implicate them in CSC biology.

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Recent approaches for isolating and culturing mouse bone marrow-derived mesenchymal stromal stem cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200708134337 ◽

2020 ◽

Vol 15 ◽

Author(s):

Basem M. Abdallah ◽

Hany M. Khattab

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Molecular Mechanisms ◽

Replicative Senescence ◽

Cellular Heterogeneity ◽

High Yield ◽

Mouse Strains ◽

Mouse Bone Marrow ◽

Differentiation Potential ◽

Stromal Stem Cells

: The isolation and culture of murine bone marrow-derived mesenchymal stromal stem cells (mBMSCs) have attracted great interest in terms of the pre-clinical applications of stem cells in tissue engineering and regenerative medicine. In addition, culturing mBMSCs is important for studying the molecular mechanisms of bone remodelling using relevant transgenic mice. Several factors have created challenges in the isolation and high-yield expansion of homogenous mBMSCs; these factors include low frequencies of bone marrow-derived mesenchymal stromal stem cells (BMSCs) in bone marrow, variation among inbred mouse strains, contamination with haematopoietic progenitor cells (HPCs), the replicative senescence phenotype and cellular heterogeneity. In this review, we provide an overview of nearly all protocols used for isolating and culturing mBMSCs with the aim of clarifying the most important guidelines for culturing highly purified mBMSC populations retaining in vitro and in vivo differentiation potential.

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