Publications by authors named "Tim Lohoff"
Article Synopsis
- The retinal therapeutics field has significantly evolved since the first anti-VEGF therapy was approved in 2004, with a focus on a variety of retinal diseases and improved treatment options, resulting in nearly $10 billion in investments over two decades.
- Treatments have shifted from competing against anti-VEGF therapies to finding ways to reduce patient treatment burden, alongside new initiatives targeting conditions like dry AMD and Retinitis pigmentosa.
- The review highlights successful drug approvals, ongoing challenges, investment dynamics, and future strategies in retinal therapeutics, including innovative approaches like cell-based therapies and gene editing.
Background: Perturbation of DNA methyltransferases (DNMTs) and of the active DNA demethylation pathway via ten-eleven translocation (TET) methylcytosine dioxygenases results in severe developmental defects and embryonic lethality. Dynamic control of DNA methylation is therefore vital for embryogenesis, yet the underlying mechanisms remain poorly understood.
Results: Here we report a single-cell transcriptomic atlas from Dnmt and Tet mutant mouse embryos during early organogenesis.
Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration.
View Article and Find Full Text PDFFormation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos.
View Article and Find Full Text PDFArticle Synopsis
- Researchers explored how cells transition into a naive pluripotent state, discovering that this process can happen through different pathways.
- One pathway involves a mesodermal state, while another resembles the early inner cell mass, leading to a greater ability to develop into various cell types.
- Both pathways eventually converge into the same naive pluripotent state, emphasizing the flexibility of these identity transitions and highlighting the essential role of the transcription factor Oct4 in regulating this process.
The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency.
View Article and Find Full Text PDFAlthough whole-genome sequencing has uncovered a large number of mutations that drive tumorigenesis, functional ratification for most mutations remains sparse. Here, we present an approach to test functional relevance of tumor mutations employing CRISPR/Cas9. Combining comprehensive sgRNA design and an efficient reporter assay to nominate efficient and selective sgRNAs, we establish a pipeline to dissect roles of cancer mutations with potential applicability to personalized medicine and future therapeutic use.
View Article and Find Full Text PDFCircadian control of gene expression is well characterized at the transcriptional level, but little is known about diel or circadian control of translation. Genome-wide translation state profiling of mRNAs in Arabidopsis thaliana seedlings grown in long day was performed to estimate ribosome loading per mRNA. The experiments revealed extensive translational regulation of key biological processes.
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