DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

Download Full-text

Emerging Potential of Exosomes on Adipogenic Differentiation of Mesenchymal Stem Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.649552 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yuxuan Zhong ◽

Xiang Li ◽

Fanglin Wang ◽

Shoushuai Wang ◽

Xiaohong Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Adipogenic Differentiation ◽

Stem Cell Differentiation ◽

Cartilage Tissue ◽

Differentiation Potential ◽

Engineering Research ◽

Adipose Tissue Engineering

The mesenchymal stem cells have multidirectional differentiation potential and can differentiate into adipocytes, osteoblasts, cartilage tissue, muscle cells and so on. The adipogenic differentiation of mesenchymal stem cells is of great significance for the construction of tissue-engineered fat and the treatment of soft tissue defects. Exosomes are nanoscale vesicles secreted by cells and widely exist in body fluids. They are mainly involved in cell communication processes and transferring cargo contents to recipient cells. In addition, exosomes can also promote tissue and organ regeneration. Recent studies have shown that various exosomes can influence the adipogenic differentiation of stem cells. In this review, the effects of exosomes on stem cell differentiation, especially on adipogenic differentiation, will be discussed, and the mechanisms and conclusions will be drawn. The main purpose of studying the role of these exosomes is to understand more comprehensively the influencing factors existing in the process of stem cell differentiation into adipocytes and provide a new idea in adipose tissue engineering research.

Download Full-text

Glioblastoma Stem Cells as a New Therapeutic Target for Glioblastoma

Clinical Medicine Insights Oncology ◽

10.4137/cmo.s30271 ◽

2015 ◽

Vol 9 ◽

pp. CMO.S30271 ◽

Cited By ~ 23

Author(s):

Rasime Kalkan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Signaling Pathways ◽

Therapeutic Target ◽

Fatal Outcome ◽

Cellular Heterogeneity ◽

Cell Phenotype ◽

Glioblastoma Stem Cells ◽

Glioblastoma Stem Cell

Primary and secondary glioblastomas (GBMs) are two distinct diseases. The genetic and epigenetic background of these tumors is highly variable. The treatment procedure for these tumors is often unsuccessful because of the cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcome of these tumors promotes researchers to find out new markers associated with the prognosis and treatment planning. In this communication, the role of glioblastoma stem cells in tumor progression and the malignant behavior of GBMs are summarized with attention to the signaling pathways and molecular regulators that are involved in maintaining the glioblastoma stem cell phenotype. A better understanding of these stem cell-like cells is necessary for designing new effective treatments and developing novel molecular strategies to target glioblastoma stem cells. We discuss hypoxia as a new therapeutic target for GBM. We focus on the inhibition of signaling pathways, which are associated with the hypoxia-mediated maintenance of glioblastoma stem cells, and the knockdown of hypoxia-inducible factors, which could be identified as attractive molecular target approaches for GBM therapeutics.

Download Full-text

Recognition of tenogenic differentiation using convolutional neural network

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-3051 ◽

2020 ◽

Vol 6 (3) ◽

pp. 200-204

Author(s):

Gözde Dursun ◽

Saurabh Balkrishna Tandale ◽

Jörg Eschweiler ◽

Mersedeh Tohidnezhad ◽

Bernd Markert ◽

...

Keyword(s):

Neural Networks ◽

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

High Performance ◽

Image Data ◽

Stem Cell Differentiation ◽

Differentiation Potential ◽

Non Invasive ◽

Invasive Cell

AbstractMethodologies to assess stem cell differentiation in the culturing state are needed for regenerative medicine and tissue engineering techniques. In recent years, convolutional neural networks (CNNs), a class of deep neural networks, have made impressive advancements in image-based classification, recognition and detection tasks. CNNs have been introduced as a non-invasive cell characterization method by learning features directly from image data of unlabeled cells. Furthermore, this approach serves as a rapid and inexpensive methodology with high performance compared to traditional techniques that require complex laboratory procedures including antibody staining and gene expression analysis. Here, we studied the potential of the CNNs approach to recognize stem cell differentiation based on cell morphology utilizing phasecontrast microscopy images.We have examined the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) into tenocytes, with the treatment of bone morphogenetic protein-12 (BMP-12). After treatment, the phase-contrast images of cells were obtained directly from cell culture flasks to train CNN and the differentiated phenotype of stem cells was characterized by immunostaining. CNN was able to classify the cells into three groups including non-stem cells (chondrocytes), stem cells (BMSCs) and differentiated stem cells (tenocytes) based on their morphology with 92.2 % accuracy. The presented study revealed that CNN performed faster and non-invasive cell classification task compared to traditional methodologies.

Download Full-text

Nanomaterials and Stem Cell Differentiation Potential: An Overview of Biological Aspects and Biomedical Efficacy

Current Medicinal Chemistry ◽

10.2174/0929867328666210712193113 ◽

2021 ◽

Vol 28 ◽

Author(s):

Ali Ehsani ◽

Asma Jodaei ◽

Mohammad Barzegar-Jalali ◽

Ezzatollah Fathi ◽

Raheleh Farahzadi ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Cellular Proliferation ◽

Biomedical Application ◽

Stem Cell Differentiation ◽

Differentiation Potential ◽

Proliferation And Differentiation ◽

Physicochemical Features ◽

Biological Aspects

: Nanoparticles (NPs) due to their medical applications are widely used. Accordingly, the use of mesenchymal stem cells is one of the most important alternatives in tissue engineering field. NPs play effective roles in stem cells proliferation and differentiation. The combination of NPs and tissue regeneration by stem cells has created new therapeutic approach towards humanity. Of note, the physicochemical properties of NPs determine their biological function. Interestingly, various mechanisms such as modulation of signaling pathways and generation of reactive oxygen species, are involved in NPs-induced cellular proliferation and differentiation. This review summarized the types of nanomaterials effective on stem cell differentiation, the physicochemical features, biomedical application of these materials and relationship between nanomaterials and environment.

Download Full-text

Cellular Heterogeneity During Embryonic Stem Cell Differentiation to Epiblast Stem Cells Is Revealed by the ShcD/RaLP Adaptor Protein

Stem Cells ◽

10.1002/stem.1217 ◽

2012 ◽

Vol 30 (11) ◽

pp. 2423-2436 ◽

Cited By ~ 13

Author(s):

Margherita Y. Turco ◽

Laura Furia ◽

Anja Dietze ◽

Luis Fernandez Diaz ◽

Simona Ronzoni ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Embryonic Stem Cell ◽

Embryonic Stem ◽

Adaptor Protein ◽

Stem Cell Differentiation ◽

Cellular Heterogeneity ◽

Embryonic Stem Cell Differentiation ◽

Epiblast Stem Cells

Download Full-text

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200512105347 ◽

2020 ◽

Vol 15 (6) ◽

pp. 531-546 ◽

Cited By ~ 1

Author(s):

Hwa-Yong Lee ◽

In-Sun Hong

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Oxidative Phosphorylation ◽

Metabolic Pathways ◽

Critical Role ◽

The Self ◽

Specific Cell ◽

Differentiation Potential ◽

Self Renewal ◽

Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

Download Full-text

Identification of cardiac stem cells with FLK1, CD31, and VE‐cadherin expression during embryonic stem cell differentiation

The FASEB Journal ◽

10.1096/fj.04-1998com ◽

2005 ◽

Vol 19 (3) ◽

pp. 371-378 ◽

Cited By ~ 38

Author(s):

Midori Iida ◽

Toshio Heike ◽

Momoko Yoshimoto ◽

Shiro Baba ◽

Hiraku Doi ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Embryonic Stem Cell ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Embryonic Stem Cell Differentiation ◽

Cardiac Stem Cells

Download Full-text

Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

Molecular and Cellular Biology ◽

10.1128/mcb.00121-15 ◽

2015 ◽

Vol 35 (10) ◽

pp. 1700-1711 ◽

Cited By ~ 15

Author(s):

Fenfang Chen ◽

Xia Lin ◽

Pinglong Xu ◽

Zhengmao Zhang ◽

Yanzhen Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Nuclear Export ◽

Stem Cell Differentiation ◽

Bmp Signaling ◽

Dependent Manner ◽

Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

Download Full-text