A multi-omic atlas of human embryonic skeletal development.

Human embryonic bone and joint formation is determined by coordinated differentiation of progenitors in the nascent skeleton. The cell states, epigenetic processes and key regulatory factors that underlie lineage commitment of these cells remain elusive. Here we applied paired transcriptional and epigenetic profiling of approximately 336,000 nucleus droplets and spatial transcriptomics to establish a multi-omic atlas of human embryonic joint and cranium development between 5 and 11 weeks after conception.

A spatial human thymus cell atlas mapped to a continuous tissue axis.

T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus-the Cortico-Medullary Axis-and used it to perform a spatially resolved analysis.

Bin2cell reconstructs cells from high resolution Visium HD data.

Summary: Visium HD by 10X Genomics is the first commercially available platform capable of capturing full scale transcriptomic data paired with a reference morphology image from archived FFPE blocks at sub-cellular resolution. However, aggregation of capture regions to single cells poses challenges. Bin2cell reconstructs cells from the highest resolution data (2 μm bins) by leveraging morphology image segmentation and gene expression information.

Molecular connectomics: Placing cells into morphological tissue context.

Here we propose "molecular connectomics" to link molecular and morphological cell features in three dimensions across scales, using machine learning and artificial intelligence to reveal emergent properties of complex biological systems.

Knockout of the longevity gene Klotho perturbs aging and Alzheimer's disease-linked brain microRNAs and tRNA fragments.

Overexpression of the longevity gene Klotho prolongs lifespan, while its knockout shortens lifespan and impairs cognition via perturbation of myelination and synapse formation. However, comprehensive analysis of Klotho knockout effects on mammalian brain transcriptomics is lacking. Here, we report that Klotho knockout alters the levels of aging- and cognition related mRNAs, long non-coding RNAs, microRNAs and tRNA fragments.