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An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models.

Nature neuroscience · 2023 · 26(1): 27-38

Huntington's disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by CAG trinucleotide expansion in exon 1 of the huntingtin (HTT) gene. Since the reduction of pathogenic mutant HTT messenger RNA is therapeutic, we developed a mutant allele-sensitive CAG^EX …

PMID 36510111 DOI ↗

Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor-Mutant Neoplasms.

Cancer discovery · 2022 · 12(3): 836-855

Mutations in splicing factors (SF) are the predominant class of mutations in myelodysplastic syndrome (MDS), but convergent downstream disease drivers remain elusive. To identify common direct targets of missplicing by mutant U2AF1 and SRSF2, we performed RNA sequencing and enhanced …

PMID 34620690 DOI ↗

Context-dependent functional compensation between Ythdf m⁶A reader proteins.

Genes & development · 2020 · 34(19-20): 1373-1391

The N6-methyladenosine (m⁶A) modification is the most prevalent post-transcriptional mRNA modification, regulating mRNA decay and splicing. It plays a major role during normal development, differentiation, and disease progression. The modification is regulated by a set of writer, eraser, and reader …

PMID 32943573 DOI ↗

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease.

Cell stem cell · 2019 · 24(6): 1006

PMID 31173705 DOI ↗

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease.

Cell stem cell · 2018 · 23(1): 123-131.e6

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers …

PMID 29979986 DOI ↗

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Stem cell reports · 2017 · 8(4): 1086-1100

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 …

PMID 28410642 DOI ↗

Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.

Molecular psychiatry · 2016 · 21(11): 1573-1588

Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined …

PMID 27698428 DOI ↗

Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.

Genome medicine · 2016 · 8(1): 94

Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human …

PMID 27655340 DOI ↗

PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.

Nature medicine · 2016 · 22(1): 37-45

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT …

PMID 26642438 DOI ↗

Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.

Circulation · 2015 · 131(14): 1278-1290

Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators with important functions in development and disease. Here, we sought to identify and functionally characterize novel lncRNAs critical for vertebrate development. By relying on human pluripotent stem cell differentiation models, …

PMID 25739401 DOI ↗

Human cytomegalovirus infection of human embryonic stem cell-derived primitive neural stem cells is restricted at several steps but leads to the persistence of viral DNA.

Journal of virology · 2014 · 88(8): 4021-39

Congenital human cytomegalovirus (HCMV) infection is a major cause of central nervous system structural anomalies and sensory impairments. It is likely that the stage of fetal development, as well as the state of differentiation of susceptible cells at the time …

PMID 24453373 DOI ↗

A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.

Cell · 2010 · 143(4): 527-39

Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system using induced pluripotent stem cells (iPSCs) …

PMID 21074045 DOI ↗

Multiple layers of molecular controls modulate self-renewal and neuronal lineage specification of embryonic stem cells.

Human molecular genetics · 2008 · 17(R1): R67-75

Elucidating the molecular changes that arise during neural differentiation and fate specification is crucial for building accurate in vitro models of neurodegenerative diseases using human embryonic stem cells (hESCs). Here we review the importance of hESCs and derived progenitors in …

PMID 18632700 DOI ↗