Biology subjects

Nagasawa, S.

Publications and source records attributed to Nagasawa, S..

5 recordsLinked to original sources

bioRxiv2024

Spatial domain analysis to estimate spatiotemporal pathological mechanisms in microenvironment with single-cell spatial omics data

Single-cell spatial omics analysis requires consideration of biological functions and mechanisms in a microenvironment. However, microenvironment analysis using bioinformatic methods is limited by the need to detect histological morphology. In this study, we developed SpatialKNife (SKNY), an image-processing-based toolkit that detects spatial domains that potentially reflect histology and extends these domains to the microenvironment. The SKNY algorithm identified tumour spatial domains from spatial transcriptomic data of breast cancer, followed by clustering of these domains, trajectory estimation, and spatial extension to the tumour microenvironment (TME). The results of the trajectory estimation were consistent with the known mechanisms of cancer progression. We observed endothelial cell and macrophage infiltration into the TME at mid-stage progression. Our results suggest that analysis using the spatial domain as a unit reflects pathological mechanisms in the TME. This approach may be applicable to the biological estimation of diverse microenvironments.

bioinformatics↗

bioRxiv2022

Can SARS-CoV-2 transmit from a dead body?

Although it has been 2.5 years since the COVID-19 pandemic began, the transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a dead infected body remains unclear, and often, in Japan bereaved family members are not allowed to view in-person a loved one who has died from COVID-19. In this study, we analyzed the possibility of SARS-CoV-2 transmission from a dead body by using the hamster model. We also analyzed the effect of Angel-care--in which the pharynx, nostril, and rectum are plugged--and embalming on reducing transmissibility from dead bodies. We found that SARS-CoV-2 could be transmitted from the body of animals that died within a few days of infection; however, Angel-care and embalming were effective in preventing transmission from the dead body. These results suggest that protection from infection is essential when in contact with a SARS-CoV-2-infected dead body, and that sealing the cavities of a dead body is an important infection control step if embalming is not done. ImportanceWe found that SARS-CoV-2 could be transmitted from a dead body presumably via postmortem gases. However, we also found that postmortem care, such as plugging the pharynx, nostrils, and rectum, or embalming could prevent transmission from the dead body. These results indicate that protection from infection is essential when handling infected corpses, and that appropriate care of SARS-CoV-2-infected corpses is important.

microbiology↗

bioRxiv2021

Intensive Single Cell Analysis Reveals Immune Cell Diversity among Healthy Individuals

It is believed that immune responses are different between individuals and at different times. In addition, personal health histories and unique environmental conditions should collectively determine the present state of immune cells. However, the cellular and molecular system mechanisms underlying such heterogeneity remain largely elusive. In this study, we conducted a systematic time-lapse single-cell analysis, using 171 single-cell libraries and 30 mass cytometry datasets intensively for seven healthy individuals. We found substantial diversity in immune cell populations and their gene expression patterns between different individuals. These patterns showed daily fluctuations even within the same individual spending a usual life. Similar diversities were also observed for the T cell receptor and B cell receptor repertoires. Detailed immune cell profiles at healthy statuses should give an essential background information to understand their immune responses, when the individual is exposed to various environmental conditions. To demonstrate this idea, we conducted the similar analysis for the same individuals on the vaccination of Influenza and SARS-CoV-2, since the date and the dose of the antigens are well-defined in these cases. In fact, we found that the distinct responses to vaccines between individuals, althougth key responses are common. Single cell immune cell profile data should make fundamental data resource to understand variable immune responses, which are unique to each individual.

genomics↗

bioRxiv2021

Efficient prediction of a spatial transcriptomics profile better characterizes breast cancer tissue sections without costly experimentation

Spatial transcriptomics is an emerging technology requiring costly reagents and considerable skills, limiting the identification of transcriptional markers related to histology. Here, we show that predicted spatial gene-expressions in unmeasured regions and tissues can enhance biologists histological interpretations. We developed the Deep learning model for Spatial gene Clusters and Expression, DeepSpaCE and confirmed its performance using the spatial-transcriptome profiles and immunohistochemistry images of consecutive human breast cancer tissue sections. For example, the predicted expression patterns of SPARC, an invasion marker, highlighted a small tumor-invasion region that is difficult to identify using raw data of spatial transcriptome alone because of a lack of measurements. We further developed semi-supervised DeepSpaCE using unlabeled histology images and increased the imputation accuracy of consecutive sections, enhancing applicability for a small sample size. Our method enables users to derive hidden histological characters via spatial transcriptome and gene annotations, leading to accelerated biological discoveries without additional experiments.

genomics↗

bioRxiv2020

Importin α2 associates with chromatin via a novel DNA binding domain

Nuclear transport of proteins is important for facilitating appropriate nuclear functions. The proteins of the importin family play key roles in nuclear transport as transport receptors for a huge number of nuclear proteins. Additionally, these proteins possess other functions, including chromatin association and gene regulation. However, these non-transport functions of importin are not yet fully understood, especially their molecular-level mechanisms for functioning with chromatin and their consequences. Here, we report the novel molecular characteristics of importin involving binding to diverse sequences in chromatin. We newly identified and characterized a DNA-binding domain--the Nucleic Acid Associating Trolley pole domain (NAAT domain)--in the N-terminal region of importin within the conventional importin {beta} binding (IBB) domain, which was shown to be necessary for nuclear transport of cargo proteins. We propose a stroll and locate model to explain the association of importin with chromatin. This is the first study to delineate the interaction between importin and chromatin DNA via the NAAT domain, indicating the bifunctionality of the importin N-terminal region for nuclear transport and chromatin association.

molecular biology↗