Biology subjects

Ouji-Sageshima, N.

Publications and source records attributed to Ouji-Sageshima, N..

3 recordsLinked to original sources

bioRxiv2022

Delayed SARS-CoV-2 Spread and Olfactory Cell Lineage Impairment in Close-Contact Infection Syrian Hamster Models

ObjectivesClose contact with patients with COVID-19 is speculated to be the most common cause of viral transmission, but the pathogenesis of COVID-19 by close contact remains to be elucidated. In addition, despite olfactory impairment being a unique complication of COVID-19, the impact of SARS-CoV-2 on the olfactory cell lineage has not been fully validated. This study aimed to elucidate close-contact viral transmission to the nose and lungs and to investigate the temporal damage in the olfactory receptor neuron (ORN) lineage caused by SARS-CoV-2. MethodsSyrian hamsters were orally administered SARS-CoV-2 as direct-infection models. On day 7 after inoculation, infected and uninfected hamsters were housed in the same cage for 30 minutes. These uninfected hamsters were subsequently assigned to a close-contact group. First, viral presence in the nose and lungs was verified in the infection and close-contact groups at several time points. Next, the impacts on the olfactory epithelium, including olfactory progenitors, immature ORNs, and mature ORNs, were examined histologically. Then, the viral transmission status and chronological changes in tissue damage were compared between the direct-infection and close-contact groups. ResultsIn the close-contact group, viral presence could not be detected in both the nose and lungs on day 3, and the virus was identified in both tissues on day 7. In the direct-infection group, the viral load was highest in the nose and lungs on day 3, decreased on day 7, and was no longer detectable on day 14. Histologically, in the direct-infection group, mature ORNs were most depleted on day 3 (p < 0.001) and showed a recovery trend on day 14, with similar trends for olfactory progenitors and immature ORNs. In the close-contact group, there was no obvious tissue damage on day 3, but on day 7, the number of all ORN lineage cells significantly decreased (p < 0.001). ConclusionSARS-CoV-2 was transmitted even after brief contact and subsequent olfactory epithelium and lung damage occurred more than 3 days after the trigger of infection. The present study also indicated that SARS-CoV-2 damages all ORN lineage cells, but this damage can begin to recover approximately 14 days post infection.

microbiology↗

bioRxiv2022

T cell responses induced by SARS-CoV-2 mRNA vaccination are associated with clonal replacement

mRNA vaccines against the Spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) elicit strong T-cell responses. However, its not known whether T cell clonotypes responding to the first vaccination repeatedly expand with booster vaccinations. Here, we temporally tracked the CD8+ T-cell repertoire in individuals who received three shots of the BNT162b2 mRNA vaccine. By analyzing the kinetic profile of CD8+ T-cell clonotypes responding to the first, second, or third shot, we demonstrated that newly expanded clonotypes elicited by the second shot replaced many of those that responded to the first shot. Although these 2nd responder clonotypes expanded after the third shot, their clonal diversity was skewed, and they were partially replaced by newly elicited the 3rd responders. Furthermore, this replacement of vaccine-responding clonotypes occurred within the same Spike epitope. These results suggest that CD8+ T-cell memory induced by repetitive mRNA vaccination is characterized by the emergence of new dominant clones.

immunology↗

bioRxiv2021

TAS-Seq: a robust and sensitive amplification method for beads-based scRNA-seq

Single-cell RNA-sequencing (scRNA-seq) is valuable for analyzing cellular heterogeneity. Cell composition accuracy is critical for analyzing cell-cell interaction networks from scRNA-seq data. We developed terminator-assisted solid-phase cDNA amplification and sequencing (TAS-Seq) for scRNA-seq based on a terminator, terminal transferase, and nanowell/bead-based scRNA-seq platform; TAS-Seq showed high tolerance to variations in the terminal transferase reaction, which complicate the handling of existing terminal transferase-based scRNA-seq methods. In murine and human lung samples, TAS-Seq yielded scRNA-seq data that were highly correlated with flow-cytometric data, showing higher gene-detection sensitivity and more robust detection of important cell-cell interactions and expression of growth factors/interleukins in cell subsets than 10X Chromium v2 and Smart-seq2. Expanding TAS-Seq application will improve understanding and atlas construction of lung biology at the single-cell level.

genomics↗