The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived neural precursor cells

Yoo, Myungsik; Carromeu, Cassiano; Kwon, Ohyoon; Muotri, Alysson R.; Schachner, Melitta

doi:10.1016/j.bbrc.2017.10.073

Cited by 16 publications

(22 citation statements)

References 29 publications

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“…The most extensive work using the iPSC model has been devoted to Rett syndrome, with the phenotypic characterization of these cell lines obtained from patients’ fibroblasts. Decreased cell soma size and neuritogenesis [ 10 ], reduced expression of the adhesion molecule L1 [ 10 ], and synaptic alterations [ 11 , 12 ] have been observed by using this model, supporting the expected defects in neuronal connectivity.…”

Section: In Vitro Use Of Human Ipsc-derived Neurons In Neurodevelopmementioning

confidence: 60%

Induced pluripotent stem cells as a tool to study brain circuits in autism-related disorders

Vitrac

Cloëz‐Tayarani

2018

Stem Cell Res Ther

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The mammalian brain is a very complex organ containing an estimated 200 billion cells in humans. Therefore, studying human brain development has become very challenging given all the data that are available from different approaches, notably genetic studies.Recent pluripotent stem cell methods have given rise to the possibility of modeling neurodevelopmental diseases associated with genetic defects. Fibroblasts from patients have been reprogrammed into pluripotent stem cells to derive appropriate neuronal lineages. They specifically include different subtypes of cortical neurons that are at the core of human-specific cognitive abilities. The use of neurons derived from induced pluripotent stem cells (iPSC) has led to deciphering convergent and pleiotropic neuronal synaptic phenotypes found in neurodevelopmental disorders such as autism spectrum disorders (ASD) and their associated syndromes. In addition to these initial studies, remarkable progress has been made in the field of stem cells, with the major objective of reproducing the in vivo maturation steps of human neurons. Recently, several studies have demonstrated the ability of human progenitors to respond to guidance cues and signals in vivo that can direct neurons to their appropriate sites of differentiation where they become fully mature neurons.We provide a brief overview on research using human iPSC in ASD and associated syndromes and on the current understanding of new theories using the re-implantation of neural precursors in mouse brain.

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Section: In Vitro Use Of Human Ipsc-derived Neurons In Neurodevelopmementioning

confidence: 60%

Induced pluripotent stem cells as a tool to study brain circuits in autism-related disorders

Vitrac

Cloëz‐Tayarani

2018

Stem Cell Res Ther

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“…All RTT studies using iPSC models have used iPSCs reprogrammed from patient-derived fibroblast cells ( Table 1 ). As RTT manifests mostly in girls, the majority of studies to date have used iPSC lines from female patients, with the exception of five studies that used male patient-specific iPSCs ( Tang et al, 2016 ; Zhang et al, 2016 ; de Souza et al, 2017 ; Yoo et al, 2017 ; Kim et al, 2019 ; Supplementary Table 1 ). To take into consideration the impact of XCI and genetic background of individuals, female lines are usually compared to their isogenic controls, which are genetically corrected iPSCs from the same patient ( Kim et al, 2011 ; Cheung et al, 2012 ; Andoh-Noda et al, 2015 ; Djuric et al, 2015 ; Chin et al, 2016 ; Landucci et al, 2018 ; Nguyen et al, 2018 ).…”

Section: Modeling Rett Syndrome Using Ipscsmentioning

confidence: 99%

“…To take into consideration the impact of XCI and genetic background of individuals, female lines are usually compared to their isogenic controls, which are genetically corrected iPSCs from the same patient ( Kim et al, 2011 ; Cheung et al, 2012 ; Andoh-Noda et al, 2015 ; Djuric et al, 2015 ; Chin et al, 2016 ; Landucci et al, 2018 ; Nguyen et al, 2018 ). In studies where male lines are used, the control cell lines have been derived from the unaffected father, acting as a surrogate isogenic control ( Tang et al, 2016 ; de Souza et al, 2017 ; Yoo et al, 2017 ; Kim et al, 2019 ).…”

Section: Modeling Rett Syndrome Using Ipscsmentioning

confidence: 99%

Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models

et al. 2021

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Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, mostly caused by mutations in MECP2. The disorder mainly affects girls and it is associated with severe cognitive and physical disabilities. Modeling RTT in neural and glial cell cultures and brain organoids derived from patient- or mutation-specific human induced pluripotent stem cells (iPSCs) has advanced our understanding of the pathogenesis of RTT, such as disease-causing mechanisms, disease progression, and cellular and molecular pathology enabling the identification of actionable therapeutic targets. Brain organoid models that recapitulate much of the tissue architecture and the complexity of cell types in the developing brain, offer further unprecedented opportunity for elucidating human neural development, without resorting to conventional animal models and the limited resource of human neural tissues. This review focuses on the new knowledge of RTT that has been gleaned from the iPSC-based models as well as limitations of the models and strategies to refine organoid technology in the quest for clinically relevant disease models for RTT and the broader spectrum of neurodevelopmental disorders.

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“…These researchers found that these mutations downregulated the ionic glutamate receptor D1 (GluD1), which is known as a synaptic adhesion molecule that maintains normal presynaptic and postsynaptic membrane stabilities . Some subsequent studies have suggested that an MECP2 mutation decreases neuron size and synapse number and affects the differentiation of glutamatergic neurons . These abnormal phenotypes can be alleviated by using insulin‐like growth factor 1 (IGF1), which interacts with IGF1/IGF1R and thyroid hormone receptor (TRalpha 3) .…”

Section: Development Of Ipsc Technologymentioning

confidence: 99%

“…38,39 Some subsequent studies have suggested that an MECP2 mutation decreases neuron size and synapse number and affects the differentiation of glutamatergic neurons. [40][41][42] These abnormal phenotypes can be alleviated by using insulin-like growth factor 1 (IGF1), which interacts with IGF1/IGF1R and thyroid hormone receptor (TRalpha 3). 43 Thus, iPSC technology has created favorable conditions for the direct study of the molecular mechanisms of human GE.…”

Section: Development Of Ipsc Technologymentioning

confidence: 99%

Progress in the molecular mechanisms of genetic epilepsies using patient‐induced pluripotent stem cells

et al. 2018

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SummaryResearch findings on the molecular mechanisms of epilepsy almost always originate from animal experiments, and the development of induced pluripotent stem cell (iPSC) technology allows the use of human cells with genetic defects for studying the molecular mechanisms of genetic epilepsy (GE) for the first time. With iPSC technology, terminally differentiated cells collected from GE patients with specific genetic etiologies can be differentiated into many relevant cell subtypes that carry all of the GE patient's genetic information. iPSCs have opened up a new research field involving the pathogenesis of GE. Using this approach, studies have found that gene mutations induce GE by altering the balance between neuronal excitation and inhibition, which is associated. among other factors, with neuronal developmental disturbances, ion channel abnormalities, and synaptic dysfunction. Simultaneously, astrocyte activation, mitochondrial dysfunction, and abnormal signaling pathway activity are also important factors in the molecular mechanisms of GE.

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The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived neural precursor cells

Cited by 16 publications

References 29 publications

Induced pluripotent stem cells as a tool to study brain circuits in autism-related disorders

Induced pluripotent stem cells as a tool to study brain circuits in autism-related disorders

Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models

Progress in the molecular mechanisms of genetic epilepsies using patient‐induced pluripotent stem cells

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