Dermatan sulphate promotes neuronal differentiation in mouse and human stem cells

Abstract Dermatan sulphate (DS), a glycosaminoglycan, is present in the extracellular matrix and on the cell surface. Previously, we showed that heparan sulphate plays a key role in the maintenance of the undifferentiated state in mouse embryonic stem cells (mESCs) and in the regulation of their differentiation. Chondroitin sulphate has also been to be important for pluripotency and differentiation of mESCs. Keratan sulphate is a marker of human pluripotent stem cells. To date, however, the function of DS in mESCs has not been clarified. Dermatan 4 sulfotransferase 1, which transfers sulphate to the C-4 hydroxyl group of N-acetylgalactosamine of DS, contributes to neuronal differentiation of mouse neural progenitor cells. Therefore, we anticipated that neuronal differentiation would be induced in mESCs in culture by the addition of DS. To test this expectation, we investigated neuronal differentiation in mESCs and human neural stem cells (hNSCs) cultures containing DS. In mESCs, DS promoted neuronal differentiation by activation of extracellular signal-regulated kinase 1/2 and also accelerated neurite outgrowth. In hNSCs, DS promoted neuronal differentiation and neuronal migration, but not neurite outgrowth. Thus, DS promotes neuronal differentiation in both mouse and human stem cells, suggesting that it offers a novel method for efficiently inducing neuronal differentiation.

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DOT1L-mediated murine neuronal differentiation associates with H3K79me2 accumulation and preserves SOX2-enhancer accessibility

Nature Communications ◽

10.1038/s41467-020-19001-7 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Francesco Ferrari ◽

Laura Arrigoni ◽

Henriette Franz ◽

Annalisa Izzo ◽

Ludmila Butenko ◽

...

Keyword(s):

Stem Cells ◽

Neuronal Differentiation ◽

Promoter Region ◽

Cellular Differentiation ◽

Neural Progenitor Cells ◽

Embryonic Stem ◽

Neural Progenitors ◽

Murine Embryonic Stem Cells ◽

Transcriptional State

Abstract During neuronal differentiation, the transcriptional profile and the epigenetic context of neural committed cells is subject to significant rearrangements, but a systematic quantification of global histone modification changes is still missing. Here, we show that H3K79me2 increases and H3K27ac decreases globally during in-vitro neuronal differentiation of murine embryonic stem cells. DOT1L mediates all three degrees of methylation of H3K79 and its enzymatic activity is critical to modulate cellular differentiation and reprogramming. In this context, we find that inhibition of DOT1L in neural progenitor cells biases the transcriptional state towards neuronal differentiation, resulting in transcriptional upregulation of genes marked with H3K27me3 on the promoter region. We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural progenitors. Our work provides evidence that DOT1L activity gates differentiation of progenitors by allowing SOX2-dependent transcription of stemness programs.

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Lack of lipid phosphate phosphatase-3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth

Developmental Dynamics ◽

10.1002/dvdy.23779 ◽

2012 ◽

Vol 241 (5) ◽

pp. 953-964 ◽

Cited By ~ 10

Author(s):

Roberto Sánchez-Sánchez ◽

Sara L. Morales-Lázaro ◽

José-Manuel Baizabal ◽

Manjula Sunkara ◽

Andrew J. Morris ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Neurite Outgrowth ◽

Neuronal Differentiation ◽

Embryonic Stem ◽

Lipid Phosphate

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Neuronal Differentiation of Cryopreserved Neural Progenitor Cells Derived from Mouse Embryonic Stem Cells

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2000.2631 ◽

2000 ◽

Vol 271 (2) ◽

pp. 418-421 ◽

Cited By ~ 36

Author(s):

Christopher R. Hancock ◽

Jonathon P. Wetherington ◽

Nevin A. Lambert ◽

Brian G. Condie

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Neural Progenitor Cells ◽

Embryonic Stem ◽

Neural Progenitor ◽

Mouse Embryonic Stem Cells

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Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

Organogenesis ◽

10.1080/15476278.2015.1011921 ◽

2014 ◽

Vol 10 (4) ◽

pp. 365-377 ◽

Cited By ~ 49

Author(s):

Leonardo D’Aiuto ◽

Yun Zhi ◽

Dhanjit Kumar Das ◽

Madeleine R Wilcox ◽

Jon W Johnson ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Large Scale ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Human Ipsc

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Dual Inhibition of Activin/Nodal/TGF-βand BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

Stem Cells International ◽

10.1155/2016/1035374 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 13

Author(s):

Vedavathi Madhu ◽

Abhijit S. Dighe ◽

Quanjun Cui ◽

D. Nicole Deal

Keyword(s):

Stem Cells ◽

Nervous System ◽

Neuronal Differentiation ◽

Adult Stem Cells ◽

Embryonic Stem ◽

Bmp Signaling ◽

Specific Marker ◽

Adipose Derived Stem Cells ◽

Neuronal Marker ◽

Dual Inhibition

Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-βand BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally,in vitrosubcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.

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Neural Repair in Stroke

Cell Transplantation ◽

10.1177/0963689719863784 ◽

2019 ◽

Vol 28 (9-10) ◽

pp. 1123-1126 ◽

Cited By ~ 4

Author(s):

Nikolas G. Toman ◽

Andrew W. Grande ◽

Walter C. Low

Keyword(s):

Stem Cells ◽

Neural Progenitor Cells ◽

Neuronal Cells ◽

Embryonic Stem ◽

Fetal Brain ◽

Neurological Deficits ◽

Experimental Stroke ◽

Neural Repair ◽

Cell Therapies ◽

Blood Stem Cells

This article reviews the progress that has been made in the development of cell therapies for the repair of nervous system damage caused by strokes, since the first report on the use of cell transplants in animal models of ischemic brain injury in 1988. At that time neural progenitor cells derived from fetal brain tissue were used as sources of cells to replace specific subsets of neuronal cells that were lost in various regions of the brain following experimentally induced strokes. Since 1988, cells from other sources, such as embryonic stem cells and inducible pluripotent stem cells, have been investigated for their ability to replace neuronal cells and repair the damaged brain. Most recently, mesenchymal stem cells and cord blood stem cells have been studied for the ability to modulate the immune system and ameliorate the neuropathology and neurological deficits associated with experimental stroke. The preclinical investigation of different cell therapy approaches for treating stroke during the past three decades has now led to many ongoing clinical trials, with the clinical evaluation of stem cell therapies for stroke now involving global participants.

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Premature neuronal differentiation in familial Alzheimer’s disease human stem cells in vitro and in postmortem brain tissue

Alzheimer s & Dementia ◽

10.1002/alz.039793 ◽

2020 ◽

Vol 16 (S3) ◽

Author(s):

Charles Arber ◽

Christopher E.J. Lovejoy ◽

Nanet Willumsen ◽

Argyro Alatza ◽

Jackie M. Casey ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Stem Cells ◽

Neuronal Differentiation ◽

Brain Tissue ◽

Postmortem Brain ◽

Human Stem Cells ◽

Familial Alzheimer’S Disease ◽

Postmortem Brain Tissue ◽

Familial Alzheimer's Disease

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Heparin and dermatan sulphate induced capacitation of frozen-thawed bull spermatozoa measured by merocyanine-540

Zygote ◽

10.1017/s0967199407004182 ◽

2007 ◽

Vol 15 (3) ◽

pp. 225-232 ◽

Cited By ~ 17

Author(s):

A.-S. Bergqvist ◽

J. Ballester ◽

A. Johannisson ◽

N. Lundeheim ◽

H. Rodríguez-Martínez

Keyword(s):

Chondroitin Sulphate ◽

Heparan Sulphate ◽

Negative Control ◽

Dermatan Sulphate ◽

Flow Cytometric ◽

Merocyanine 540 ◽

Incubation Duration ◽

Flow Cytometric Study ◽

Oviductal Fluid

SummaryGlycosaminoglycans (GAGs) are present in the oviduct in which the major part of sperm capacitation occurs. In this study we have tested how capacitation of frozen-thawed bull spermatozoa is effected by exposure to different GAGs detectable or possibly present in oviductal fluid; i.e. heparin, hyaluronan, heparan sulphate, dermatan sulphate and chondroitin sulphate. Following exposure of different duration, the spermatozoa were stained with either Chlortetracycline (CTC) or merocyanine-540 and evaluated with epifluorescent light microscopy or flow cytometry, respectively. Heparin elicited a significant increase in the number of alive, capacitated spermatozoa, either expressed as higher merocyanine-540 fluorescence (p < 0.0001) or as B-pattern (p = 0.0021) in the CTC assay, during 4 h of incubation. When comparing the different GAG treatments one by one to the negative control in the flow cytometric study, only heparin and dermatan sulphate were significant (p < 0.0001) higher than the control at 0–30 min of incubation. Duration of incubation did not affect the proportion of capacitated spermatozoa when measured as merocyanine-540 fluorescence or CTC B-pattern, but the length of the incubation did affect the number of dead (Yo-PRO 1 positive) spermatozoa (p < 0.0001). Exposure to zona pellucida proteins significantly increased the proportion of acrosome reacted spermatozoa (p = 0.016). Both heparin and dermatan sulphate induce capacitation of frozen-thawed bull spermatozoa in vitro.

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