scholarly journals Ntrk1 mutation co-segregating with bipolar disorder and inherited kidney disease in a multiplex family causes defects in neuronal growth and depression-like behavior in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kazuo Nakajima ◽  
Alannah Miranda ◽  
David W. Craig ◽  
Tatyana Shekhtman ◽  
Stanislav Kmoch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bipolar Disorder ◽  
Pluripotent Stem Cells ◽  
Tail Suspension Test ◽  
Multiplex Family ◽  
Genome Wide ◽  
The Family ◽  
Induced Pluripotent ◽  
Inherited Kidney Disease ◽  
The Brain

AbstractPreviously, we reported a family in which bipolar disorder (BD) co-segregates with a Mendelian kidney disorder linked to 1q22. The causative renal gene was later identified as MUC1. Genome-wide linkage analysis of BD in the family yielded a peak at 1q22 that encompassed the NTRK1 and MUC1 genes. NTRK1 codes for TrkA (Tropomyosin-related kinase A) which is essential for development of the cholinergic nervous system. Whole genome sequencing of the proband identified a damaging missense mutation, E492K, in NTRK1. Induced pluripotent stem cells were generated from family members, and then differentiated to neural stem cells (NSCs). E492K NSCs had reduced neurite outgrowth. A conditional knock-in mouse line, harboring the point mutation in the brain, showed depression-like behavior in the tail suspension test following challenge by physostigmine, a cholinesterase inhibitor. These results are consistent with the cholinergic hypothesis of depression. They imply that the NTRK1 E492K mutation, impairs cholinergic neurotransmission, and may convey susceptibility to bipolar disorder.

scholarly journals Pluripotent Stem Cells: Current Understanding and Future Directions

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Antonio Romito ◽  
Gilda Cobellis
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Human Embryos ◽  
Pluripotent Cell ◽  
Future Directions ◽  
The Family ◽  
Induced Pluripotent ◽  
Early Mouse ◽  
Distinct Features

Pluripotent stem cells have the ability to undergo self-renewal and to give rise to all cells of the tissues of the body. However, this definition has been recently complicated by the existence of distinct cellular states that display these features. Here, we provide a detailed overview of the family of pluripotent cell lines derived from early mouse and human embryos and compare them with induced pluripotent stem cells. Shared and distinct features of these cells are reported as additional hallmark of pluripotency, offering a comprehensive scenario of pluripotent stem cells.

scholarly journals Advancing Knowledge of Down Syndrome Brain Development and Function With Human Stem Cells

2020 ◽  
Vol 125 (2) ◽  
pp. 90-92
Author(s):  
Anita Bhattacharyya
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Brain Development ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Stem Cells ◽  
Down Syndrome Brain ◽  
Induced Pluripotent ◽  
The Brain ◽  
Disease Specific

Abstract Our bodies are made up of over 250 specific cell types, and all initially arise from stem cells during embryonic development. Stem cells have two characteristics that make them unique: (1) they are pluripotent, meaning that they can differentiate into all cell types of the body, and (2) they are capable of self-renewal to generate more of themselves and are thus able to populate an organism. Human pluripotent stem cells were first isolated from human embryos twenty years ago (Thomson et al., 1998) and more recently, technology to reprogram somatic cells, such as skin and blood, to induced pluripotent stem cells has emerged (Park et al., 2008; Takahashi et al., 2007; Yu et al., 2007). Induced pluripotent stem cells, or iPSCs, are particularly valuable as disease specific iPSCs can be generated from individuals with specific genetic mutations diseases. Researchers have harnessed the power of stem cells to understand many aspects of developmental biology in model organisms (e.g. worms, mice) and more recently, in humans. Human stem cells in culture recapitulate development. For example, formation of the brain occurs prenatally and follows a specific pattern of timing and cell generation. Human stem cells in the culture dish follow a similar pattern when exposed to developmental cues and can thus be used to understand aspects of prenatal human brain development that are not accessible by other means. Disease-specific iPSCs are a valuable tool to model neural development in specific neurodevelopmental disorders like Down syndrome. Down syndrome is a classic developmental disorder; mistakes that are made during development of a particular organ system result in the characteristics of the disorder. In the brain, mistakes during prenatal brain development lead to intellectual disability. Trisomy 21 (Ts21) iPSCs generated from somatic cells of Down syndrome individuals may enable us to understand the mistakes made during Down syndrome brain development.

scholarly journals Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142693 ◽  
Author(s):  
Kwi Hye Kim ◽  
Jiangang Liu ◽  
Rachelle J. Sells Galvin ◽  
Jeffrey L. Dage ◽  
Janice A. Egeland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bipolar Disorder ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Transcriptomic Analysis ◽  
Old Order Amish ◽  
Old Order ◽  
Induced Pluripotent

scholarly journals Non-immunogenic Induced Pluripotent Stem Cells, a Promising Way Forward for Allogenic Transplantations for Neurological Disorders

2021 ◽  
Vol 2 ◽  
Author(s):  
Henriette Reventlow Frederiksen ◽  
Ulrik Doehn ◽  
Pernille Tveden-Nyborg ◽  
Kristine K. Freude
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neurological Disorders ◽  
Developmental Disorders ◽  
Gene Editing ◽  
Current Status ◽  
Cell Replacement ◽  
Induced Pluripotent ◽  
The Brain

Neurological disorder is a general term used for diseases affecting the function of the brain and nervous system. Those include a broad range of diseases from developmental disorders (e.g., Autism) over injury related disorders (e.g., stroke and brain tumors) to age related neurodegeneration (e.g., Alzheimer's disease), affecting up to 1 billion people worldwide. For most of those disorders, no curative treatment exists leaving symptomatic treatment as the primary mean of alleviation. Human induced pluripotent stem cells (hiPSC) in combination with animal models have been instrumental to foster our understanding of underlying disease mechanisms in the brain. Of specific interest are patient derived hiPSC which allow for targeted gene editing in the cases of known mutations. Such personalized treatment would include (1) acquisition of primary cells from the patient, (2) reprogramming of those into hiPSC via non-integrative methods, (3) corrective intervention via CRISPR-Cas9 gene editing of mutations, (4) quality control to ensure successful correction and absence of off-target effects, and (5) subsequent transplantation of hiPSC or pre-differentiated precursor cells for cell replacement therapies. This would be the ideal scenario but it is time consuming and expensive. Therefore, it would be of great benefit if transplanted hiPSC could be modulated to become invisible to the recipient's immune system, avoiding graft rejection and allowing for allogenic transplantations. This review will focus on the current status of gene editing to generate non-immunogenic hiPSC and how these cells can be used to treat neurological disorders by using cell replacement therapy. By providing an overview of current limitations and challenges in stem cell replacement therapies and the treatment of neurological disorders, this review outlines how gene editing and non-immunogenic hiPSC can contribute and pave the road for new therapeutic advances. Finally, the combination of using non-immunogenic hiPSC and in vivo animal modeling will highlight the importance of models with translational value for safety efficacy testing; before embarking on human trials.

scholarly journals Genome Wide Profiling of Dopaminergic Neurons Derived from Human Embryonic and Induced Pluripotent Stem Cells

2014 ◽  
Vol 23 (4) ◽  
pp. 406-420 ◽  
Author(s):  
Olga Momčilović ◽  
Qiuyue Liu ◽  
Andrzej Swistowski ◽  
Tatiane Russo-Tait ◽  
Yiqiang Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Dopaminergic Neurons ◽  
Genome Wide ◽  
Induced Pluripotent
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