Biology subjects

Raichur, R.

Publications and source records attributed to Raichur, R..

3 recordsLinked to original sources

bioRxiv2025

Tissue architecture dynamics underlying immune development and decline in the thymus

The age-associated decline in adaptive immune function, widely observed in vertebrates, has been attributed to thymic involution. To gain insights into the structural and transcriptional changes underlying this phenomenon, we employed high-resolution spatial transcriptomics and T-cell receptor (TCR) sequencing in mice. By analyzing 21 thymus samples spanning mouse lifespan, we uncovered significant alterations in thymic organization, including disrupted T cell development and the emergence of B cell aggregates. We also observed age- related changes in cell-cell interactions, marked by increased antigen-presenting cell presence in thymic medullary regions and a shift from inflammatory to suppressive macrophages, fostering an immunosuppressive niche. Furthermore, aged thymus tissues exhibited an abundance of regions with reduced TCR diversity, accompanied by distinct changes to gene expression profiles. Our study establishes a valuable reference for understanding aging-related alterations in adaptive immunity, revealing mechanisms underlying age-induced immunological decline.

immunology↗

bioRxiv2024

Aging disrupts spatiotemporal coordination in the cycling ovary

Throughout the female reproductive lifespan, the ovary completes hundreds of cycles of follicle development, ovulation, and tissue regeneration1-3. These processes rely on the precisely coordinated intricate multicellular interactions across time and space4. How aging disrupts these interactions, leading to an overall decline in reproductive and endocrine functions, remains understudied. To understand the multicellular dynamics that underlie ovarian function and their changes with age, here we use Slide-seq, a near-cellular spatial transcriptomics method, to profile 22 mouse ovaries across the reproductive cycle and chronological age, representing 610,620 near-cellular spots across 69 spatial transcriptomic profiles5,6. We develop a segmentation analysis to identify spatial niches that capture different states of folliculogenesis from static snapshots in situ, allowing us to examine the multicellular dynamics of 358 oocytes, 668 follicles, and 236 corpora lutea. We find that aging disrupts both the spatial organization and temporal coordination of folliculogenesis before the cessation of cycling, which may contribute to the dysregulation of hormone production and signaling. These disruptions are marked by altered immune cell dynamics, inflammatory signaling, and global tissue disorganization that impair the cyclic remodeling required for ovarian function. Our findings reveal how multicellular niches orchestrate ovarian function and demonstrate how age-related breakdown of tissue organization across time and space precedes reproductive decline.

genomics↗

bioRxiv2023

Slide-tags: scalable, single-nucleus barcoding for multi-modal spatial genomics

Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed. Missing from these measurements, however, is the ability to routinely and easily spatially localise these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 micron spatial resolution, and delivered whole-transcriptome data that was indistinguishable in quality from ordinary snRNA-seq. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil, and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualised receptor-ligand interactions driving B-cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to virtually any single-cell measurement technology. As proof of principle, we performed multiomic measurements of open chromatin, RNA, and T-cell receptor sequences in the same cells from metastatic melanoma. We identified spatially distinct tumour subpopulations to be differentially infiltrated by an expanded T-cell clone and undergoing cell state transition driven by spatially clustered accessible transcription factor motifs. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.

genomics↗