Publications by authors named "Gary Dixon"
Tau aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia. There are disease-causing variants of the tau-encoding gene, , and the presence of tau aggregates is highly correlated with disease progression. However, the molecular mechanisms linking pathological tau to neuronal dysfunction are not well understood due to our incomplete understanding of the normal functions of tau in development and aging and how these processes change in the context of causal disease variants of tau.
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- Tau protein aggregation is linked to neurodegenerative diseases such as Alzheimer's and frontotemporal dementia, with certain neuron types being particularly vulnerable.
- Researchers used a genome-wide CRISPRi screen in neurons derived from induced pluripotent stem cells (iPSCs) to identify various cellular factors that influence tau accumulation, discovering both expected pathways like autophagy and unexpected ones like UFMylation.
- The study highlights the role of the E3 ubiquitin ligase CUL5 in regulating tau levels and shows how mitochondrial dysfunction impacts tau processing, suggesting new therapeutic targets for combating tauopathies.
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- The pancreas and liver both originate from a shared group of progenitor cells, but how they differentiate from the foregut is unclear.
- A study used various advanced techniques to investigate this differentiation, discovering that the transcription factor HHEX is crucial for pancreatic development and acts as a guard against other cell fates.
- HHEX works alongside other transcription factors (FOXA1, FOXA2, GATA4) to ensure cells commit to the pancreatic lineage, preventing them from becoming liver or duodenum cells instead.
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- Changes in DNA methylation are essential for normal heart development, and altered patterns can lead to congenital heart disease.
- TET enzymes are critical for DNA demethylation and the differentiation of cardiomyocytes from human embryonic stem cells; without them, cardiomyocyte generation fails.
- TET activity influences the methylation status of key genes, affecting WNT signaling and cardiac progenitor specification, which are vital for proper heart development.
DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to discover DNA methylation regulators.
View Article and Find Full Text PDFHuman embryonic stem cells (ESCs) and human induced pluripotent stem cells hold great promise for cell-based therapies and drug discovery. However, homogeneous differentiation remains a major challenge, highlighting the need for understanding developmental mechanisms. We performed genome-scale CRISPR screens to uncover regulators of definitive endoderm (DE) differentiation, which unexpectedly uncovered five Jun N-terminal kinase (JNK)-JUN family genes as key barriers of DE differentiation.
View Article and Find Full Text PDFThe mir-34/449 family consists of six homologous miRNAs at three genomic loci. Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated epithelia suggest a functional significance in ciliogenesis. Here we report that mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality, infertility and strong respiratory dysfunction caused by defective mucociliary clearance.
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