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CRISPR Activator Approaches Assayed in Human Stem Cells, Neurons

For a paper in Molecular Cell, a team from the Wellcome Sanger Institute and other centers in the UK and China share findings from a barcoded reporter-based analysis of CRISPR activation (CRISPRa) activity in human induced pluripotent stem cells (iPSCs) or differentiated neurons. Starting with iPSCs or neurons containing thousands of barcoded receptor sequences peppered randomly across the genome, the researchers used targeted amplicon sequencing to assess a CRISPRa efficacy in the presence of "dead" Cas9 enzymes paired with a transcriptionally activating VPR domain or chromatin-modifying p300 protein sequence, bringing in RNA sequencing-based expression profiles and chromatin immunoprecipitation sequencing profiles focused on half a dozen chromatin modifications. The analyses pointed to molecular influencing dCas9-VPR or dCas9-p300 activity in each cell type, particularly chromatin-dependent activity, that was assessed further with single-cell experiments and single-cell RNA-seq. "Our data demonstrate, for the first time, that dCas9-VPR-mediated transcriptional activation is generally applicable across chromatin states and cell types, but that basal expression level and chromatin state can impact both the degree of activation and its variability" the authors report. "These features will be important in the design and analysis of CRISPRa screens and the use of these systems for disease modeling or therapeutic intervention."

The Scan

ChatGPT Does As Well As Humans Answering Genetics Questions, Study Finds

Researchers in the European Journal of Human Genetics had ChatGPT answer genetics-related questions, finding it was about 68 percent accurate, but sometimes gave different answers to the same question.

Sequencing Analysis Examines Gene Regulatory Networks of Honeybee Soldier, Forager Brains

Researchers in Nature Ecology & Evolution find gene regulatory network differences between soldiers and foragers, suggesting bees can take on either role.

Analysis of Ashkenazi Jewish Cohort Uncovers New Genetic Loci Linked to Alzheimer's Disease

The study in Alzheimer's & Dementia highlighted known genes, but also novel ones with biological ties to Alzheimer's disease.

Tara Pacific Expedition Project Team Finds High Diversity Within Coral Reef Microbiome

In papers appearing in Nature Communications and elsewhere, the team reports on findings from the two-year excursion examining coral reefs.