Affichage des articles dont le libellé est iPSC. Afficher tous les articles
Affichage des articles dont le libellé est iPSC. Afficher tous les articles

16 août 2019

Génération de sept lignées iPSC à partir de cellules mononucléées du sang périphérique pouvant être utilisées pour étudier les "troubles du spectre de l'autisme"

Aperçu: G.M.
Nous avons généré et caractérisé sept lignées de cellules souches pluripotentes induites par l'homme (iPSC) dérivées de cellules mononucléées du sang périphérique (PBMC) appartenant à une seule famille, y compris des personnes non atteintes et affectées cliniquement diagnostiquées avec un "trouble du spectre de l'autisme" (dTSA). La reprogrammation des PBMC a été réalisée à l'aide du virus Sendai non intégratif contenant les facteurs de reprogrammation POU5F1 (OCT4), SOX2, KLF4 et MYC. 
Toutes les lignées iPSC présentaient un caryotype normal et la pluripotence était validée par immunofluorescence, cytométrie en flux et leur capacité à se différencier dans les trois couches germinales embryonnaires. 
Ces lignées iPSC constituent une ressource précieuse pour l’étude des mécanismes moléculaires sous-jacents des TSA.

2019 Aug 1;39:101516. doi: 10.1016/j.scr.2019.101516.

Generation of seven iPSC lines from peripheral blood mononuclear cells suitable to investigate Autism Spectrum Disorder

Author information

1
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
2
Department of Paediatrics, University of Melbourne, Parkville, Australia; Murdoch Children's Research Institute, Parkville, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
3
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Victorian Clinical Genetics Services, Victoria, Australia.
4
Victorian Clinical Genetics Services, Victoria, Australia.
5
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia.
6
Olga Tennison Autism Research Centre, School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
7
Murdoch Children's Research Institute, Parkville, Australia.
8
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
9
Department of Paediatrics, University of Melbourne, Parkville, Australia; Department of Medicine, University of Melbourne, Austin Health, Melbourne, VIC, Australia; Florey Institute, Melbourne, VIC, Australia; Department of Neurology, Royal Children's Hospital, Melbourne, Australia.
10
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia. Electronic address: paul.lockhart@mcri.edu.au

Abstract

We have generated and characterized seven human induced pluripotent stem cell (iPSC) lines derived from peripheral blood mononuclear cells (PBMCs) from a single family, including unaffected and affected individuals clinically diagnosed with Autism Spectrum Disorder (ASD). The reprogramming of the PBMCs was performed using non-integrative Sendai virus containing the reprogramming factors POU5F1 (OCT4), SOX2, KLF4 and MYC. All iPSC lines exhibited a normal karyotype and pluripotency was validated by immunofluorescence, flow cytometry and their ability to differentiate into the three embryonic germ layers. These iPSC lines are a valuable resource to study the molecular mechanisms underlying ASD.
PMID:31415975
DOI:10.1016/j.scr.2019.101516

13 juin 2017

Comprendre les troubles du développement neurologique à l'aide de neurones humains dérivés de cellules souches pluripotentes

Aperçu: G.M.
La recherche sur les troubles psychiatriques a longtemps été entravée par l'absence de modèles appropriés. Les cellules souches pluripotentes induites (iPSC) offrent une source illimitée de cellules spécifiques au patient, qui en principe peuvent être différenciées dans tous les types de cellules somatiques pertinentes pour la maladie afin de créer des modèles in vitro du trouble visé.
Ici, les protocoles de différenciation neuronale disponibles à cette fin et les progrès actuels sur les modèles de schizophrénie, les "troubles du spectre de l'autisme" et le trouble bipolaire basés sur l'iPSC ont été examinés. 

Brain Pathol. 2017 Jul;27(4):508-517. doi: 10.1111/bpa.12517.

Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons

Author information

1
Neuroscience and Mental Health Research Institute, School of Medicine and School of Biosciences, Cardiff University, Cardiff, United Kingdom.

Abstract

Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference "control" hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments.
PMID:28585386
DOI:10.1111/bpa.12517