scholarly journals Tectal stem cells display diverse regenerative capacities

2018 ◽  
Author(s):  
Benjamin W. Lindsey ◽  
Georgia E. Aitken ◽  
Jean K. Tang ◽  
Mitra Khabooshan ◽  
Celia Vandestadt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Marginal Zone ◽  
Post Injury ◽  
Differentiation Potential ◽  
Radial Glial ◽  
Newborn Neurons ◽  
Glial Fate ◽  
Regenerate Tissue ◽  
Dickkopf 1

AbstractHow diverse adult stem and progenitor populations regenerate tissue following damage to the CNS remains unknown across most neurogenic domains. To understand the role of quiescent radial-glial (qRG) stem cells during regeneration, we tested the hypothesis that qRG could be induced to proliferate and produce newborn neurons. We designed a stab lesion assay in the midbrain tectum of the adult zebrafish to target an isolated population of qRG, and investigated their proliferative behaviour, differentiation potential, and requirement of Wnt/β-catenin signalling for the regenerative response. EdU-labelling showed that a small proportion of qRG transit to a proliferative state (pRG), but that progeny of pRG are restricted to a radial-glial fate. Lesion promoted upregulation of proliferation and neurogenesis from neuro-epithelial-like amplifying progenitors (NE-Ap) of the tectal marginal zone (TMZ). Homeostatic levels of Wnt/β-catenin signalling persisted under lesioned conditions in the qRG/pRG population, whereby increased β-catenin staining and axin2 expression was present in the NE-Ap progenitor zone. Attenuation of Wnt signalling using Dickkopf-1, demonstrated that proliferative responses post-injury appeared to be Wnt-independent. Our results align with the emerging view that adult stem/progenitor phenotypes are characterized by discrete, rather than mutual, regenerative programs and that different stem cell domains employ different modes of regeneration.

scholarly journals MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kulisara Marupanthorn ◽  
Chairat Tantrawatpan ◽  
Pakpoom Kheolamai ◽  
Duangrat Tantikanlayaporn ◽  
Sirikul Manochantr
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Osteogenic Differentiation ◽  
Differentiation Potential ◽  
Osteogenic Gene Expression ◽  
Osteogenic Gene

AbstractMesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.

scholarly journals Metabolic Phenotyping of Adipose-Derived Stem Cells Reveals a Unique Signature and Intrinsic Differences between Fat Pads

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Camille Lefevre ◽  
Baptiste Panthu ◽  
Danielle Naville ◽  
Sylvie Guibert ◽  
Claudie Pinteur ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Metabolic Diseases ◽  
Environmental Changes ◽  
Metabolic Phenotype ◽  
Mitochondrial Activity ◽  
Differentiation Potential ◽  
Adipose Tissues ◽  
Fat Pads

White adipose tissues are functionally heterogeneous and differently manage the excess of energy supply. While the expansion of subcutaneous adipose tissues (SAT) is protective in obesity, that of visceral adipose tissues (VAT) correlates with the emergence of metabolic diseases. Maintained in fat pads throughout life, adipose stem cells (ASC) are mesenchymal-like stem cells with adipogenesis and multipotent differentiation potential. ASC from distinct fat pads have long been reported to present distinct proliferation and differentiation potentials that are maintained in culture, yet the origins of these intrinsic differences are still unknown. Metabolism is central to stem cell fate decision in line with environmental changes. In this study, we performed high-resolution nuclear magnetic resonance (NMR) metabolomic analyses of ASC culture supernatants in order to characterize their metabolic phenotype in culture. We identified and quantified 29 ASC exometabolites and evaluated their consumption or secretion over 72 h of cell culture. Both ASC used glycolysis and mitochondrial metabolism, as evidenced by the high secretions of lactate and citrate, respectively, but V-ASC mostly used glycolysis. By varying the composition of the cell culture medium, we showed that glutaminolysis, rather than glycolysis, supported the secretion of pyruvate, alanine, and citrate, evidencing a peculiar metabolism in ASC cells. The comparison of the two types of ASC in glutamine-free culture conditions also revealed the role of glutaminolysis in the limitation of pyruvate routing towards the lactate synthesis, in S-ASC but not in V-ASC. Altogether, our results suggest a difference between depots in the capacity of ASC mitochondria to assimilate pyruvate, with probable consequences on their differentiation potential in pathways requiring an increased mitochondrial activity. These results highlight a pivotal role of metabolic mechanisms in the discrimination between ASC and provide new perspectives in the understanding of their functional differences.

scholarly journals Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells

2021 ◽  
Author(s):  
Seong Min Kim ◽  
Eun-Ji Kwon ◽  
Yun-Jeong Kim ◽  
Young-Hyun Go ◽  
Ji-Young Oh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Erk Signaling ◽  
Differentiation Potential ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Pluripotency Maintenance

Abstract The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency. Loss of Shp2 increased naive pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus replacing the use of iMek1 not only for maintenance but also for the establishment of naïve ESCs through reprogramming. Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency.

Age-associated changes in microRNAs affect the differentiation potential of human mesenchymal stem cells: Novel role of miR-29b-1-5p expression

Bone ◽  
2021 ◽  
pp. 116154
Author(s):  
Nada H. Eisa ◽  
Periyasamy T. Sudharsan ◽  
Sergio Mas Herrero ◽  
Samuel A. Herberg ◽  
Brian F. Volkman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Differentiation Potential

scholarly journals Bone Marrow Mesenchymal Stem Cells Regulate IL-4 and INF-γ Expression in AR Mouse Model

2020 ◽  
Author(s):  
Chuanliang Zhao ◽  
Jingwen Sun ◽  
Xiaojing Cai ◽  
Wentao Zou ◽  
Jiaxiong Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Th1 Cell ◽  
Differentiation Potential ◽  
Th2 Cell ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Bone marrow mesenchymal stem cells can promote the recovery of immune balance and regulate the balance of Th1/2 cells. Allergic rhinitis is a disease with Th1/2 imbalance mediated by IgE. It’s unclear whether BMSCs could regulate AR disease. In this study, the possible role of BMSCs was explored. Methods : AR mouse model was established by ovalbumin (OVA). 18 models were randomly divided into three groups: AR-sensitized, Stem-cell-returned, Medium-returned; six unsensitized mouses named normal-control. IgE, IL-4 and INF-γ levels were measured by Elisa. Observing migration of BMSCs by immunofluorescence. Flow cytometry used to detect changes of Th1/2. STAT 4/6 protein level was detected by Western-blot. Results : After OVA-sensitization, IgE, IL-4 and STAT6 levels were higher, INF-γ and STAT4 level was lower. Flow cytometry revealed a decrease in Th1 cell and an increase in Th2 cell in AR group. After BMSCs treatment, t IgE, IL-4 and STAT6 levels in SCRg and MRg were lower than that in AR group, and tINF-γ and STAT4 level were higher than hat inAR group. Flow cytometry showed that the content of Th1 cell increased while Th2 cell decreased. Conclusions: BMSCs return treatment could decrease the expression of IL-4, promote the expression of INF-γ and regulate the balance of Th cell, and the mechanism was closely related to STAT4/6 signaling pathway. However there was no statistical difference between SCRg and MRg, so the role of BMSCs maybe achieved through paracrine function rather than multi-directional differentiation potential.

scholarly journals Laser-Based Propagation of Human iPS and ES Cells Generates Reproducible Cultures with Enhanced Differentiation Potential

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kristi A. Hohenstein Elliott ◽  
Cory Peterson ◽  
Anuradha Soundararajan ◽  
Natalia Kan ◽  
Brandon Nelson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Discovery ◽  
Regenerative Medicine ◽  
Es Cells ◽  
Human Escs ◽  
Differentiation Potential ◽  
Novel Approach ◽  
Mechanical Devices

Proper maintenance of stem cells is essential for successful utilization of ESCs/iPSCs as tools in developmental and drug discovery studies and in regenerative medicine. Standardization is critical for all future applications of stem cells and necessary to fully understand their potential. This study reports a novel approach for the efficient, consistent expansion of human ESCs and iPSCs using laser sectioning, instead of mechanical devices or enzymes, to divide cultures into defined size clumps for propagation. Laser-mediated propagation maintained the pluripotency, quality, and genetic stability of ESCs/iPSCs and led to enhanced differentiation potential. This approach removes the variability associated with ESC/iPSC propagation, significantly reduces the expertise, labor, and time associated with manual passaging techniques and provides the basis for scalable delivery of standardized ESC/iPSC lines. Adoption of standardized protocols would allow researchers to understand the role of genetics, environment, and/or procedural effects on stem cells and would ensure reproducible production of stem cell cultures for use in clinical/therapeutic applications.

scholarly journals Dual Role of MSC-Derived Exosomes in Tumor Development

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Rou Zhao ◽  
Xinke Chen ◽  
Hui Song ◽  
Qingli Bie ◽  
Bin Zhang
Keyword(s):  
Stem Cells ◽  
Information Exchange ◽  
Adult Stem Cells ◽  
Tumor Development ◽  
Tumor Cell Growth ◽  
Differentiation Potential ◽  
Promote Tumor Growth ◽  
Tumor Growth And Metastasis ◽  
Two Sides

Mesenchymal stem cells (MSCs) are a class of adult stem cells derived from the mesoderm. They can self-renew, have multidirectional differentiation potential, and can differentiate into a variety of mesenchymal tissues. MSCs can produce a large number of exosomes, which can mediate information exchange and transmission between cells in the tumor microenvironment under conditions of rest or stress. Recent studies have reported conflicting findings regarding the effect of MSC-derived exosomes on tumors. Some studies have suggested that MSC-derived exosomes can promote tumor growth and metastasis, but others have reported that they can inhibit tumor cell growth. Here, we investigate the two sides of the debate regarding the effect of MSC-derived exosomes on tumors and analyze the reasons for the divergent findings.

scholarly journals PS1 - 158 The Role of LIN28A in Neoplastic Transformation of Human Embryonic Stem Cells (hESCs)

2016 ◽  
Vol 43 (S4) ◽  
pp. S10-S10
Author(s):  
R. Kaur ◽  
L. Liang ◽  
T. Werbowetski-Ogilvie
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Rna Binding ◽  
Embryonic Stem ◽  
Neoplastic Transformation ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Human Cancers

Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.

scholarly journals Role of Fzd6 in Regulating the Osteogenic Differentiation of Adipose-derived Stem Cells in Osteoporosis

2021 ◽  
Author(s):  
Tianli Wu ◽  
Zhihao Yao ◽  
Gang Tao ◽  
Fangzhi Lou ◽  
Hui Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Wnt Signaling Pathway ◽  
Osteogenic Potential ◽  
Adipose Derived Stem Cells ◽  
Alizarin Red ◽  
Differentiation Potential

Abstract Objective: Although it has been demonstrated that adipose-derived stem cells (ASCs) from osteoporosis mice (OP-ASCs) exhibit impaired osteogenic differentiation potential, the molecular mechanism has not yet been elucidated. We found that Fzd6 was decreased in OP-ASCs compared with ASCs. This study investigates the effects and underlying mechanisms of Fzd6 in the osteogenic potential of OP-ASCs. Methods: Fzd6 expression in ASCs and OP-ASCs was measured by PCR gene chip. Fzd6 overexpression and silencing lentiviruses were used to evaluate the role of Fzd6 in the osteogenic differentiation of OP-ASCs. Real-time PCR (qPCR) and western blotting (WB) was performed to detect the expression of Fzd6 and bone-related molecules, including runt-related transcription factor 2 (Runx2) and osteopontin (Opn). Alizarin red staining and Alkaline phosphatase (ALP) staining was performed following osteogenic induction. Microscopic CT (Micro-CT), hematoxylin and eosin staining (H&E) staining, and Masson staining were used to assess the role of Fzd6 in osteogenic differentiation of osteoporosis (OP) mice in vivo.Results: Expression of Fzd6 was decreased significantly in OP-ASCs. Fzd6 silencing down-regulated the osteogenic ability of OP-ASCs in vitro. Overexpression of Fzd6 rescued the impaired osteogenic capacity in OP-ASCs in vitro. We obtained similar results in vivo.Conclusions: Fzd6 plays an important role in regulating the osteogenic ability of OP-ASCs both in vivo and in vitro. Overexpression of Fzd6 associated with the Wnt signaling pathway promotes the osteogenic ability of OP-ASCs, which provides new insights for the prevention and treatment of OP.

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