Utilisation de cellules souches pluripotentes induites pour enquêter sur les troubles psychiatriques génétiques complexes

Aperçu: G.M.

Les cellules souches pluripotentes induites (iPSC) peuvent être générées à partir d'échantillons de tissus de patients humains, différenciés en tout type de cellules somatiques et étudiés dans des conditions de culture contrôlées. Nous examinons comment les iPSC sont utilisés pour étudier les facteurs génétiques et les mécanismes biologiques sous-jacents aux troubles psychiatriques et les considérations pour synthétiser les données entre les études.

Les résultats des études iPSC spécifiques au patient révèlent souvent des phénotypes cellulaires compatibles avec les études post-mortem et d'imagerie cérébrale.  

Les résultats imprévisibles illustrent le pouvoir des iPSC en tant qu'outil de découverte, mais peuvent aussi être attribuables à des limitations dans la modélisation de réseaux neuronaux dynamiques ou à la difficulté d'identifier le sous-type neuronal ou la phase de développement la plus touchée.

Curr Behav Neurosci Rep. 2016 Dec;3(4):275-284. doi: 10.1007/s40473-016-0100-7. Epub 2016 Oct 14.

Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders

Temme SJ¹, Maher BJ², Christian KM³.

Author information

1

Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

2

Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

3

Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

PURPOSE OF REVIEW:

Induced pluripotent stem cells (iPSCs) can be generated from human patient tissue samples, differentiated into any somatic cell type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies.

RECENT FINDINGS:

Results from patient specific-iPSC studies often reveal cellular phenotypes consistent with postmortem and brain imaging studies. Unpredicted findings illustrate the power of iPSCs as a discovery tool, but may also be attributable to limitations in modeling dynamic neural networks or difficulty in identifying the most affected neural subtype or developmental stage.

SUMMARY:

Technological advances in differentiation protocols and organoid generation will enhance our ability to model the salient pathology underlying psychiatric disorders using iPSCs. The field will also benefit from context-driven interpretations of iPSC studies that recognize all potential sources of variability, including differences in patient symptomatology, genetic risk factors and affected cellular subtype.

PMID: 28191386

PMCID: PMC5295811  [Available on 2017-12-01]

DOI: 10.1007/s40473-016-0100-7