Genome conformation is central to gene control but challenging to interrogate. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the yield of ...conformation-informative reads by over 10-fold and lowers the input requirement over 100-fold relative to that of ChIA-PET. HiChIP of cohesin reveals multiscale genome architecture with greater signal-to-background ratios than those of in situ Hi-C.
Modern transient surveys have begun discovering and following supernovae (SNe) shortly after first light-providing systematic measurements of the rise of Type II SNe. We explore how analytic models ...of early shock-cooling emission from core-collapse SNe can constrain the progenitor's radius, explosion velocity, and local host extinction. We simulate synthetic photometry in several realistic observing scenarios; assuming the models describe the typical explosions well, we find that ultraviolet observations can constrain the progenitor's radius to a statistical uncertainty of 10%-15%, with a systematic uncertainty of 20%. With these observations the local host extinction (AV) can be constrained to a factor of two and the shock velocity to 5% with a systematic uncertainty of 10%. We also reanalyze the SN light curves presented by Garnavich et al. (2016) and find that KSN 2011a can be fit by a blue supergiant model with a progenitor radius of , while KSN 2011d can be fit with a red supergiant model with a progenitor radius of . Our results do not agree with those of Garnavich et al. Moreover, we re-evaluate their claims and find that there is no statistically significant evidence for a shock-breakout flare in the light curve of KSN 2011d.
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging ...from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
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•Profiling of 10 human skin SCCs and matched normals via scRNA-seq, ST, and MIBI•Tumor-specific keratinocytes (TSKs) reside within a fibrovascular niche at leading edges•Distinct ligand-receptor and spatial niche associations for tumor and stromal cells.•Subpopulation essential tumorigenic gene networks defined by in vivo CRISPR screening
Integration of high-dimensional multi-omics approaches to characterize human cutaneous squamous cell carcinoma identifies a tumor-specific keratinocyte population as well as the immune infiltrates and heterogeneity at tumor leading edges.
ABSTRACT As new facilities come online, the astronomical community will be provided with extremely large data sets of well-sampled light curves (LCs) of transients. This motivates systematic studies ...of the LCs of supernovae (SNe) of all types, including the early rising phase. We performed unsupervised k-means clustering on a sample of 59 R-band SN II LCs and find that the rise to peak plays an important role in classifying LCs. Our sample can be divided into three classes: slowly rising (II-S), fast rise/slow decline (II-FS), and fast rise/fast decline (II-FF). We also identify three outliers based on the algorithm. The II-FF and II-FS classes are disjoint in their decline rates, while the II-S class is intermediate and "bridges the gap." This may explain recent conflicting results regarding II-P/II-L populations. The II-FS class is also significantly less luminous than the other two classes. Performing clustering on the first two principal component analysis components gives equivalent results to using the full LC morphologies. This indicates that Type II LCs could possibly be reduced to two parameters. We present several important caveats to the technique, and find that the division into these classes is not fully robust. Moreover, these classes have some overlap, and are defined in the R band only. It is currently unclear if they represent distinct physical classes, and more data is needed to study these issues. However, we show that the outliers are actually composed of slowly evolving SN IIb, demonstrating the potential of such methods. The slowly evolving SNe IIb may arise from single massive progenitors.
Here, we present Perturb-ATAC, a method that combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells based on the simultaneous ...detection of CRISPR guide RNAs and open chromatin sites by assay of transposase-accessible chromatin with sequencing (ATAC-seq). We applied Perturb-ATAC to transcription factors (TFs), chromatin-modifying factors, and noncoding RNAs (ncRNAs) in ∼4,300 single cells, encompassing more than 63 genotype-phenotype relationships. Perturb-ATAC in human B lymphocytes uncovered regulators of chromatin accessibility, TF occupancy, and nucleosome positioning and identified a hierarchy of TFs that govern B cell state, variation, and disease-associated cis-regulatory elements. Perturb-ATAC in primary human epidermal cells revealed three sequential modules of cis-elements that specify keratinocyte fate. Combinatorial deletion of all pairs of these TFs uncovered their epistatic relationships and highlighted genomic co-localization as a basis for synergistic interactions. Thus, Perturb-ATAC is a powerful strategy to dissect gene regulatory networks in development and disease.
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•A method to measure CRISPR perturbations and chromatin state in single cells•Mapping of dynamic chromatin regulatory networks through intercellular variation•Elucidating principles of epistatic interaction between trans-factors•Perturb-ATAC screen of TF function in epidermal differentiation trajectories
Perturb-ATAC combines CRISPR screening with chromatin accessibility profiling of single cells to uncover regulators of chromatin architecture and regulator occupancy and to determine epistatic relationships between regulatory factors in cell fate decisions.
This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, ...asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma.
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