scholarly journals Palmitoylation of BMPR1a regulates neural stem cell fate

2019 ◽  
Vol 116 (51) ◽  
pp. 25688-25696
Author(s):  
Thomas Wegleiter ◽  
Kilian Buthey ◽  
Daniel Gonzalez-Bohorquez ◽  
Martina Hruzova ◽  
Muhammad Khadeesh bin Imtiaz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Genetic Manipulation ◽  
Bmp Signaling ◽  
Lipid Modification ◽  
Postnatal Brain ◽  
Stem Cell Fate ◽  
Lipid Modifications ◽  
Protein Receptor

Neural stem cells (NSCs) generate neurons and glial cells throughout embryonic and postnatal brain development. The role of S-palmitoylation (also referred to as S-acylation), a reversible posttranslational lipid modification of proteins, in regulating the fate and activity of NSCs remains largely unknown. We used an unbiased screening approach to identify proteins that are S-acylated in mouse NSCs and showed that bone morphogenic protein receptor 1a (BMPR1a), a core mediator of BMP signaling, is palmitoylated. Genetic manipulation of S-acylated sites affects the localization and trafficking of BMPR1a and leads to altered BMP signaling. Strikingly, defective palmitoylation of BMPR1a modulates NSC function within the mouse brain, resulting in enhanced oligodendrogenesis. Thus, we identified a mechanism regulating the behavior of NSCs and provided the framework to characterize dynamic posttranslational lipid modifications of proteins in the context of NSC biology.

scholarly journals Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

2020 ◽  
Vol 21 (17) ◽  
pp. 6181
Author(s):  
Sara Cruciani ◽  
Giuseppe Garroni ◽  
Francesca Balzano ◽  
Renzo Pala ◽  
Emanuela Bellu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Vitamin D ◽  
Stem Cell ◽  
Cell Fate ◽  
Adipogenic Differentiation ◽  
Adipose Derived Stem Cells ◽  
Vitamin D Metabolism ◽  
Stem Cell Fate ◽  
Cellular Phenotypes

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.

scholarly journals NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 973
Author(s):  
Tullia Maraldi ◽  
Cristina Angeloni ◽  
Cecilia Prata ◽  
Silvana Hrelia
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Immune Modulation ◽  
Ex Vivo ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Human Stem Cells ◽  
Stem Cell Fate

One of the major sources of reactive oxygen species (ROS) generated within stem cells is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (NOXs), which are critical determinants of the redox state beside antioxidant defense mechanisms. This balance is involved in another one that regulates stem cell fate: indeed, self-renewal, proliferation, and differentiation are decisive steps for stem cells during embryo development, adult tissue renovation, and cell therapy application. Ex vivo culture-expanded stem cells are being investigated for tissue repair and immune modulation, but events such as aging, senescence, and oxidative stress reduce their ex vivo proliferation, which is crucial for their clinical applications. Here, we review the role of NOX-derived ROS in stem cell biology and functions, focusing on positive and negative effects triggered by the activity of different NOX isoforms. We report recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment and discuss the implications in ex vivo expansion and in vivo engraftment, function, and longevity. This review highlights the role of NOX as a pivotal regulator of several stem cell populations, and we conclude that these aspects have important implications in the clinical utility of stem cells, but further studies on the effects of pharmacological modulation of NOX in human stem cells are imperative.

scholarly journals EBF1 is expressed in pericytes and contributes to pericyte cell commitment

2021 ◽  
Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Cell Lineage ◽  
Cell Maturation ◽  
Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

scholarly journals The dynamic role of bone morphogenetic proteins in neural stem cell fate and maturation

2012 ◽  
Vol 72 (7) ◽  
pp. 1068-1084 ◽  
Author(s):  
Allison M. Bond ◽  
Oneil G. Bhalala ◽  
John A. Kessler
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Bone Morphogenetic Proteins ◽  
Stem Cell Fate

Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Human Blood ◽  
Asymmetric Cell Division ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

scholarly journals The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

2019 ◽  
Vol 106 ◽  
pp. 49-56 ◽  
Author(s):  
Natalia Sánchez-Romero ◽  
Pilar Sainz-Arnal ◽  
Iris Pla-Palacín ◽  
Pablo Royo Dachary ◽  
Helen Almeida ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Dynamic Relationship ◽  
Health And Disease

scholarly journals N6-Methyladenosine in RNA and DNA: An Epitranscriptomic and Epigenetic Player Implicated in Determination of Stem Cell Fate

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Pengfei Ji ◽  
Xia Wang ◽  
Nina Xie ◽  
Yujing Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Direct Interaction ◽  
Limited Information ◽  
Stem Cell Fate ◽  
Base Modification ◽  
Dna And Rna ◽  
Proliferation And Differentiation

Vast emerging evidences are linking the base modifications and determination of stem cell fate such as proliferation and differentiation. Among the base modification markers extensively studied, 5-methylcytosine (5-mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as important epigenetic markers involved in regulation of cellular biological processes. N6-Methyladenosine modification in DNA (m6dA), mRNA (m6A), tRNA, and other noncoding RNAs has been defined as another important epigenetic and epitranscriptomic marker in eukaryotes in recent years. The mRNA m6A modification has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (m6A writer), demethylases (m6A eraser), and direct interaction proteins (readers), while limited information on the DNA m6dA is available. The levels and the landscapes of m6A in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the lifespan. Additionally, progress has been made in appreciation of the link between aberrant m6A modification in stem cells and diseases, like cancers and neurodegenerative disorders. These achievements are inspiring scientists to further uncover the epigenetic mechanisms for stem cell development and to dissect pathogenesis of the multiple diseases conferred by development aberration of the stem cells. This review article will highlight the research advances in the role of m6A methylation modifications of DNA and RNA in the regulation of stem cell and genesis of the closely related disorders. Additionally, this article will also address the research directions in the future.

scholarly journals Regulation and Directing Stem Cell Fate by Tissue Engineering Functional Microenvironments: Scaffold Physical and Chemical Cues

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Fei Xing ◽  
Lang Li ◽  
Changchun Zhou ◽  
Cheng Long ◽  
Lina Wu ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Fate ◽  
Chemical Cues ◽  
Physical Factors ◽  
Stem Cell Fate ◽  
Physical And Chemical

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

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