Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures.

Single-cell RNA sequencing studies have revealed the heterogeneity of cell states present in the rheumatoid arthritis (RA) synovium. However, it remains unclear how these cell types interact with one another and how synovial microenvironments shape observed cell states. Here, we use spatial transcriptomics (ST) to define stable microenvironments across eight synovial tissue samples from six RA patients and characterize the cellular composition of ectopic lymphoid structures (ELS).

Racial discrimination and adverse childhood experiences predicting depressive symptoms and developmental assets: Testing cultural socialization and preparation for bias as moderators among Black adolescents and caregivers.

The current study examined whether adverse childhood experiences and racial discrimination predicted adolescents' internal developmental assets, external developmental assets, and depressive symptoms. We also tested whether these relations were buffered by aspects of caregivers' reports of ethnic-racial socialization efforts (i.e.

ChromaFold predicts the 3D contact map from single-cell chromatin accessibility.

Identifying cell-type-specific 3D chromatin interactions between regulatory elements can help decipher gene regulation and interpret disease-associated non-coding variants. However, achieving this resolution with current 3D genomics technologies is often infeasible given limited input cell numbers. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps, including regulatory interactions, from single-cell ATAC sequencing (scATAC-seq) data alone.

Predictors of Progressing Toward Lifestyle Change Among Participants of an Interprofessional Lifestyle Medicine Program.

Background: Therapeutic lifestyle change can be challenging, and not every attempt is successful.

Purpose: To identify predictors of making progress toward lifestyle change among patients who participate in a lifestyle medicine program.

Methods: This was a single-center, retrospective cohort study of 205 adults who enrolled in a goal-directed, individualized, interprofessional lifestyle medicine program.

Predictors of Patient Engagement With an Interprofessional Lifestyle Medicine Program.

Background: Changes in lifestyle habits can reduce morbidity and mortality, but not everyone who can benefit from lifestyle intervention is ready to do so.

Purpose: To describe characteristics of patients who did and did not engage with a lifestyle medicine program, and to identify predictors of engagement.

Methods: This was a single-center, retrospective cohort study of 276 adult patients who presented for consultation to a goal-directed, individualized, interprofessional lifestyle medicine program.

Chronic interferon-stimulated gene transcription promotes oncogene-induced breast cancer.

The MRE11 complex (comprising MRE11, RAD50, and NBS1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic mutant mouse strain ( ) was highly susceptible to oncogene-induced breast cancer. Here we used a mammary organoid system to examine which MRE11-dependent responses are tumor-suppressive.

Generative artificial intelligence as a source of breast cancer information for patients: Proceed with caution.

Background: This study evaluated the accuracy, clinical concordance, and readability of the chatbot interface generative pretrained transformer (ChatGPT) 3.5 as a source of breast cancer information for patients.

Methods: Twenty questions that patients are likely to ask ChatGPT were identified by breast cancer advocates.

CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant.

Functional enhancer annotation is critical for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants. However, unbiased enhancer discovery in disease-relevant contexts remains challenging. To identify enhancers pertinent to diabetes, we conducted a CRISPR interference (CRISPRi) screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system.

An epigenetically distinct HSC subset supports thymic reconstitution.

Hematopoietic stem cells (HSCs) with multilineage potential are critical for effective T cell reconstitution and restoration of the adaptive immune system after allogeneic Hematopoietic Cell Transplantation (allo-HCT). The Kit subset of HSCs is enriched for multipotential precursors, but their T-cell lineage potential has not been well-characterized. We therefore studied the thymic reconstituting and T-cell potential of Kit HSCs.

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer.

Transposable elements (TEs) are abundant in the human genome, and they provide the sources for genetic and functional diversity. The regulation of TEs expression and their functional consequences in physiological conditions and cancer development remain to be fully elucidated. Previous studies suggested TEs are repressed by DNA methylation and chromatin modifications.

Noise Reduction and Localization Accuracy in a Mobile Magnetoencephalography System.

Magnetoencephalography (MEG) non-invasively provides important information about human brain electrophysiology. The growing use of optically pumped magnetometers (OPM) for MEG, as opposed to fixed arrays of cryogenic sensors, has opened the door for innovation in system design and use cases. For example, cryogenic MEG systems are housed in large, shielded rooms to provide sufficient space for the system dewar.

Thetis cells induce food-specific Treg cell differentiation and oral tolerance.

The intestinal immune system must establish tolerance to food antigens to prevent onset of allergic and inflammatory diseases. Peripherally generated regulatory T (pTreg) cells play an essential role in suppressing inflammatory responses to allergens; however, the antigen-presenting cell (APC) that instructs food-specific pTreg cells is not known. Here, we show that antigen presentation and TGF-β activation by a subset of RORγt antigen-presenting cells (APC), Thetis cells IV (TC IV), is required for food-induced pTreg cell differentiation and oral tolerance.

CRISPR Screening Uncovers a Long-Range Enhancer for in Pancreatic Differentiation and Links a Diabetes Risk Variant.

Functional enhancer annotation is a valuable first step for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants for investigation. However, unbiased enhancer discovery in physiologically relevant contexts remains a major challenge. To discover regulatory elements pertinent to diabetes, we conducted a CRISPR interference screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system.

Scalable and unbiased sequence-informed embedding of single-cell ATAC-seq data with CellSpace.

Standard scATAC sequencing (scATAC-seq) analysis pipelines represent cells as sparse numeric vectors relative to an atlas of peaks or genomic tiles and consequently ignore genomic sequence information at accessible loci. Here we present CellSpace, an efficient and scalable sequence-informed embedding algorithm for scATAC-seq that learns a mapping of DNA k-mers and cells to the same space, to address this limitation. We show that CellSpace captures meaningful latent structure in scATAC-seq datasets, including cell subpopulations and developmental hierarchies, and can score transcription factor activities in single cells based on proximity to binding motifs embedded in the same space.

ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity.

To gain insight into how ERG translocations cause prostate cancer, we performed single cell transcriptional profiling of an autochthonous mouse model at an early stage of disease initiation. Despite broad expression of ERG in all prostate epithelial cells, proliferation was enriched in a small, stem-like population with mixed-luminal basal identity (called intermediate cells). Through a series of lineage tracing and primary prostate tissue transplantation experiments, we find that tumor initiating activity resides in a subpopulation of basal cells that co-express the luminal genes and (called Basal) but not in the larger population of classical + luminal cells.

Tumour size predicts risk of recurrence in tall cell subtype papillary thyroid carcinoma.

Background: The tall cell subtype of papillary thyroid cancer (TCPTC) is the most common aggressive subtype and often treated aggressively. This approach may not be necessary in smaller tumours without adverse histological characteristics.

Methods: 97 patients with TCPTC defined as a height-to-width ratio of ≥3:1 and at least 30% tall cells were compared against 390 classical papillary thyroid carcinoma (CPTC) based on tumour size with recurrence free survival (RFS) as the primary outcome.

Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis.

We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene-peak correlations and dependence on peak calling. SCARlink outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across high-coverage multi-ome datasets while giving comparable to improved performance on low-coverage datasets.

Multicenter integrated analysis of noncoding CRISPRi screens.

The ENCODE Consortium's efforts to annotate noncoding cis-regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, noncoding CRISPR screens offer a systematic approach to investigate cis-regulatory mechanisms. The ENCODE4 Functional Characterization Centers conducted 108 screens in human cell lines, comprising >540,000 perturbations across 24.

Transcriptomic Evidence of a Link between Cell Wall Biogenesis, Pathogenesis, and Vigor in Walnut Root and Trunk Diseases.

Crown gall disease (), crown/root rot disease ( spp.), root lesion disease () and tree vigor are key traits affecting the productivity and quality of walnuts in California. Unchallenged hybrid rootstocks were analyzed by RNA-seq to examine pre-formed factors affecting these traits.