Biology subjects

Rashmi, S.

Publications and source records attributed to Rashmi, S..

3 recordsLinked to original sources

bioRxiv2023

Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions

Despite the large number of publicly available single-cell datasets, there is a limited understanding of the distinct resident immune cells and their concomitant features in diverse human organs. To address this, we compiled a dataset of 114,275 CD45+ immune cells from 14 organs from healthy donors. Although the transcriptome of immune cells is constant across organs, organ-specific gene expression changes were detected revealing unique expression in certain organs (GTPX3 in kidney, DNTT and ACVR2B in thymus). These alterations are associated with different transcriptional factor activities and pathways including metabolism. TNF- signaling through the NFkB pathway was found in various organs and immune compartments including distinct expression profiles of NFkB family genes and their target genes such as cytokines indicating their role in cell positioning. Taken together, immune cells not only protect the organs but also adapt to the host organ environment and contribute to its function and homeostasis.

immunology↗

bioRxiv2022

An Atlas of Cells in the Human Tonsil

Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we present a comprehensive census of cell types forming the human tonsil by applying single-cell transcriptome, epigenome, proteome and adaptive immune repertoire sequencing as well as spatial transcriptomics, resulting in an atlas of >357,000 cells. We provide a glossary of 121 annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is a reference map to understand alterations observed in disease. Here, we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.

immunology↗

bioRxiv2020

Ageing and MPTP- sensitivity depend on molecular and ultrastructural signatures of astroglia and microglia in mice nigra

Both astroglia and microglia show region-specific distribution in CNS and often maladapt to age-associated alterations within their niche. Studies on autopsied substantia nigra (SN) of Parkinsons disease (PD) patients and experimental models propose gliosis as a trigger for neuronal loss. Epidemiological studies propose an ethnic bias in PD prevalence, since Caucasians are more susceptible than non-whites. Similarly, different mice strains are variably sensitive to MPTP. We had earlier likened divergent MPTP-sensitivity of C57BL/6J and CD-1 mice with differential susceptibility to PD, based on the numbers of SN neurons. Here, we examined whether the variability was incumbent to inter-strain differences in glial features of male C57BL/6J and CD-1 mice. Stereological counts showed relatively more microglia and fewer astrocytes in the SN of normal C57BL/6J mice, suggesting persistence of an immune-vigilant state. MPTP-induced microgliosis and astrogliosis in both strains, suggests their involvement in pathogenesis. ELISA of pro-inflammatory cytokines in the ventral-midbrain revealed augmentation of TNF- and IL-6 at middle-age in both strains that reduced at old-age, suggesting middle-age as a critical, inflamm-aging associated time-point. TNF- levels were high in C57BL/6J, through aging and post-MPTP; while IL-6 and IL-1{beta} were upregulated at old-age. CD-1 had higher levels of anti-inflammatory cytokine TGF-{beta}. MPTP-challenge caused upregulation of enzymes MAO-A, MAO-B and iNOS in both strains. Post-MPTP enhancement in fractalkine and hemeoxygenase-1; may be neuron-associated compensatory signals. Ultrastructural observations of elongated astroglial/microglial mitochondria vis-a-vis the shrunken ones in neurons, suggest a scale-up of their functions with neurotoxic consequences. Thus, astroglia and microglia modulate aging and PD-susceptibility. HighlightsO_LISubstantia nigra of C57BL/6J and CD-1 show no baseline differences in glial numbers C_LIO_LIBoth mice show age and MPTP-induced gliosis in the substantia nigra pars compacta C_LIO_LICD-1 nigra has lower levels of pro- and higher levels of anti-inflammatory cytokines C_LIO_LITilt of balance between pro- and anti-inflammatory cytokines begins at middle age C_LIO_LIAstrocytes and microglia show elongated mitochondria and intact ER upon MPTP-injection C_LI

neuroscience↗