Subject collection: Stem Cells
- Silencing of CCR4-NOT complex subunits affects heart structure and function
Summary: Genome-wide association studies combined with in vitro human cardiac cell assays and a model organism suitable for heart studies in vivo connect CNOT1, CNOT7 and overall the CCR4-NOT complex to human heart disease and morbidity.
- Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells
Summary: Here, we generated a GNRH1-reporter cell line in hPSCs and investigated transcriptomes of GNRH1-expressing neurons and their progenitors, potentially leading to validation of new genes related to GnRH neuron function.
- Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
Summary: This Review discusses approaches to deal with and reduce cellular heterogeneity in induced pluripotent stem cell-based studies, enabling experiments to be reproducible and meaningful.
- Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs
Summary: The authors describe a neuronal model to investigate how mutations in the copper transporter ATP7A cause axonal degeneration in the peripheral nervous system.
- Inducible SMARCAL1 knockdown in iPSC reveals a link between replication stress and altered expression of master differentiation genes
Summary: This study reports the generation of an iPSC model to investigate phenotypic changes associated with loss of SMARCAL1, as found in severe forms of the genetic disease Schimke immuno-osseous dysplasia.
- mTOR hyperactivity mediates lysosomal dysfunction in Gaucher's disease iPSC-neuronal cells
Summary: Using neuronopathic Gaucher's disease iPSCs, this study has identified the mTOR complex as a potential therapeutic target in GBA1-associated neurodegeneration.
- C9ORF72-related cellular pathology in skeletal myocytes derived from ALS-patient induced pluripotent stem cells
Summary: Evidence of protein aggregation and mitochondrial dysfunction were found in skeletal myocytes differentiated from ALS-patient induced pluripotent stem cells with the C9ORF72 mutation.
- Genetic variation in GNB5 causes bradycardia by augmenting the cholinergic response via increased acetylcholine-activated potassium current (IK,ACh)
Summary: The authors show hiPSC-cardiomyocyte-based modeling of a mutation in a G-protein β-subunit that affects the electrophysiological response of cardiomyocytes to the cholinergic regulation of the heart rate, uncovering a potential therapy for severe bradycardia in humans carrying these mutations.
- Modeling blood diseases with human induced pluripotent stem cells
Summary: This Review discusses the applications of human iPSCs as preclinical models of cell and gene therapy for inherited monogenic blood disorders, as well as their more recent use as models of myeloid malignancies.
- Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model
Editor's choice: This study describes a novel 3D cell culture model that recapitulates key features of neuropathology in synucleinopathies, including large, nuclear-associated α-synuclein and ubiquitin-positive inclusions.