Mark Denham
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View article: BRD1 haploinsufficiency alters early neuronal programming and disrupts maturation in human induced glutamatergic neurons
BRD1 haploinsufficiency alters early neuronal programming and disrupts maturation in human induced glutamatergic neurons Open
BRD1 is an epigenetic regulator implicated in neurodevelopmental and psychiatric disorders, yet its role in human neuronal differentiation, maturation, and function remains poorly understood. Here we show that BRD1 haploinsufficiency disru…
View article: MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity
MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity Open
Lewy pathology, consisting of Lewy bodies and Lewy neurites, is the pathological hallmark of synucle-inopathies such as Parkinson’s disease and dementia with Lewy bodies, but it is generally thought to represent late-stage pathological cha…
View article: APP and its intracellular domain modulate Alzheimer’s disease risk gene networks in transgenic<i>APPsw</i>and<i>PSEN1M146I</i>porcine models
APP and its intracellular domain modulate Alzheimer’s disease risk gene networks in transgenic<i>APPsw</i>and<i>PSEN1M146I</i>porcine models Open
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most frequent cause of dementia. The disease has a substantial genetic component comprising both highly penetrant familial mutations ( APP , PSEN1, and PSEN2 ) an…
View article: The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation
The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation Open
Pattern recognition receptors (PRRs) induce host defense but can also induce exacerbated inflammatory responses. This raises the question of whether other mechanisms are also involved in early host defense. Using transcriptome analysis of …
View article: Protocol for generating reproducible miniaturized controlled midbrain organoids
Protocol for generating reproducible miniaturized controlled midbrain organoids Open
Here, we present a protocol for generating miniaturized controlled midbrain organoids (MiCOs) of reproducible size and cellular composition, without a necrotic center. We describe steps for maintaining and passaging human pluripotent stem …
View article: A Circular RNA Expressed from the FAT3 Locus Regulates Neural Development
A Circular RNA Expressed from the FAT3 Locus Regulates Neural Development Open
Circular RNAs (circRNAs) are key regulators of cellular processes, are abundant in the nervous system, and have putative regulatory roles during neural differentiation. However, the knowledge about circRNA functions in brain development is…
View article: Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming
Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming Open
Stellate cells are principal neurons in the entorhinal cortex that contribute to spatial processing. They also play a role in the context of Alzheimer’s disease as they accumulate Amyloid beta early in the disease. Producing human stellate…
View article: Enhanced Production of Mesencephalic Dopaminergic Neurons from Lineage-Restricted Human Undifferentiated Stem Cells
Enhanced Production of Mesencephalic Dopaminergic Neurons from Lineage-Restricted Human Undifferentiated Stem Cells Open
The differentiation of human pluripotent stem cells (hPSCs) into mesencephalic dopaminergic (mesDA) neurons requires a precise combination of extrinsic factors that recapitulates the in vivo environment and timing. Current methods are capa…
View article: Optimized Transgene Delivery Using Third‐Generation Lentiviruses
Optimized Transgene Delivery Using Third‐Generation Lentiviruses Open
The lentivirus system enables efficient genetic modification of both dividing and non‐dividing cells and therefore is a useful tool for elucidating developmental processes and disease pathogenesis. The development of third‐generation lenti…
View article: MicroRNAs and Ascl1 facilitate direct conversion of porcine fibroblasts into induced neurons
MicroRNAs and Ascl1 facilitate direct conversion of porcine fibroblasts into induced neurons Open
Direct neuronal conversion describes the process of generating induced neurons from somatic cells such as fibroblasts by overexpressing cell type-specific transcription factors, microRNAs or by culturing in the presence of small molecules.…
View article: Rapid generation of regionally specified CNS neurons by sequential patterning and conversion of human induced pluripotent stem cells
Rapid generation of regionally specified CNS neurons by sequential patterning and conversion of human induced pluripotent stem cells Open
The differentiation of patient-specific induced pluripotent stem cells (iPSCs) into specific neuronal subtypes has been exploited as an approach for modeling a variety of neurological disorders. However, achieving a highly pure population …
View article: Generation of an induced pluripotent stem cell line (DANi-011A) from a Parkinson's disease patient with a LRRK2 p.G2019S mutation
Generation of an induced pluripotent stem cell line (DANi-011A) from a Parkinson's disease patient with a LRRK2 p.G2019S mutation Open
We generated an induced pluripotent stem cell (iPSC) line from fibroblasts of a clinically diagnosed 70 year old female Parkinson's disease (PD) patient heterozygous for a pathogenic missense variant (p.G2019S; c. 6055 G > A) in the leucin…
View article: Transcriptomic profiling of porcine pluripotency identifies species-specific reprogramming requirements for culturing iPSCs
Transcriptomic profiling of porcine pluripotency identifies species-specific reprogramming requirements for culturing iPSCs Open
Porcine embryonic and induced pluripotent stem cells (ESCs; iPSCs) have proven difficult to derive and maintain in vitro. This may be due to inappropriate culturing conditions and incomplete activation of proper pluripotency networks. To t…
View article: A Modified Monomeric Red Fluorescent Protein Reporter for Assessing CRISPR Activity
A Modified Monomeric Red Fluorescent Protein Reporter for Assessing CRISPR Activity Open
Gene editing in human embryonic stem cells (hESCs) has been significantly enhanced by the discovery and development of CRISPR Cas9, a programmable nuclease system that can introduce targeted double-stranded breaks. The system relies on the…
View article: Central and Peripheral Nervous System Progenitors Derived from Human Pluripotent Stem Cells Reveal a Unique Temporal and Cell-Type Specific Expression of PMCAs
Central and Peripheral Nervous System Progenitors Derived from Human Pluripotent Stem Cells Reveal a Unique Temporal and Cell-Type Specific Expression of PMCAs Open
The P-type ATPases family consists of ion and lipid transporters. Their unique diversity in function and expression is critical for normal development. In this study we investigated human pluripotent stem cells (hPSC) and different neural …