Biology subjects

Tomita, N.

Publications and source records attributed to Tomita, N..

3 recordsLinked to original sources

bioRxiv2026

Integrating spatial and single-cell multi-omics analysis of induced pluripotent stem cell-derived cervical adenocarcinoma model

Human papillomavirus 18 (HPV18) preferentially infects cervical stem cell-like cells and is strongly associated with adenocarcinoma. However, the mechanisms underlying differentiation into cervical adenocarcinoma remain unclear due to the lack of appropriate experimental models. We aimed to establish a model of HPV18-associated cervical adenocarcinoma and elucidate its molecular and cellular differentiation mechanisms. HPV18 E6/E7 were introduced into induced pluripotent stem cell-derived reserve cell-like cells (iRCs) to generate tumor models. Spatial transcriptomics and single-cell multi-omics analyses were performed to integrate histological and molecular data. A distinct component (Gland_A) exhibited morphological and immunohistochemical features of cervical adenocarcinoma and was efficiently induced in iRC-18 tumors. Gland_A showed increased chromatin accessibility and elevated expression of FOXA1, FOXA2, and ALDH1A1. Analysis of clinical samples confirmed enrichment of ALDH1A1 in HPV-associated adenocarcinomas. This model recapitulates key features of HPV18-associated cervical adenocarcinoma and provides insights into its differentiation mechanisms.

cancer biology↗

bioRxiv2024

T-scope V4: miniaturized microscope for optogenetic tagging in freely behaving animals

A miniaturized microscope (i.e., miniscope) enables the imaging of neuronal activity using calcium sensors while simultaneously manipulating that activity using opsins in freely moving animals. However, many miniscopes use light-emitting diodes with broadband emission, leading to unintentional opsin stimulation by light intended solely for calcium sensor activation (a phenomenon referred to as "biological crosstalk"). To address this issue, we previously developed a miniscope including a port for chosen light sources, such as lasers, by restructuring the open-source UCLA Miniscope v3. However, targeting the same neuronal soma for both excitable opsin stimulation and calcium sensor imaging remained a challenge. Here, we integrated features from the UCLA Miniscope v4 into our new T-scope V4 miniscope. In optogenetic tagging experiments, we demonstrated that a 445-nm blue laser can be used to image neuronal activity with the calcium sensor GCaMP6s without inadvertently stimulating the ChrimsonR opsin, allowing for simultaneous neuronal activity imaging and manipulation in freely moving mice. Thus, the T-scope V4 can serve as a powerful tool for probing causal relationships between neuronal activity and its function in living animals. HighlightsO_LIWe developed the T-scope V4 that integrates features of the UCLA Miniscope v4 C_LIO_LIThis miniscope prevents "biological crosstalk" between sensors and opsins C_LIO_LIThis tool can help probe causal brain-behavior relationships in living animals C_LI

neuroscience↗

bioRxiv2018

Comprehensive Analysis of Indels in Whole-genome Microsatellite Regions and Microsatellite Instability across 21 Cancer Types

Microsatellites are repeats of 1-6bp units and [~]10 million microsatellites have been identified across the human genome. Microsatellites are vulnerable to DNA mismatch errors, and have thus been used to detect cancers with mismatch repair deficiency. To reveal the mutational landscape of the microsatellite repeat regions at the genome level, we analyzed approximately 20.1 billion microsatellites in 2,717 whole genomes of pan-cancer samples across 21 tissue types. Firstly, we developed a new insertion and deletion caller (MIMcall) that takes into consideration the error patterns of different types of microsatellites. Among the 2,717 pan-cancer samples, our analysis identified 31 samples, including colorectal, uterus, and stomach cancers, with higher microsatellite mutation rate ([≥] 0.03), which we defined as microsatellite instability (MSI) cancers in genome-wide level. Next, we found 20 highly-mutated microsatellites that can be used to detect MSI cancers with high sensitivity. Third, we found that replication timing and DNA shape were significantly associated with mutation rates of the microsatellites. Analysis of germline variation of the microsatellites suggested that the amount of germline variations and somatic mutation rates were correlated. Lastly, analysis of mutations in mismatch repair genes showed that somatic SNVs and short indels had larger functional impact than germline mutations and structural variations. Our analysis provides a comprehensive picture of mutations in the microsatellite regions, and reveals possible causes of mutations, as well as provides a useful marker set for MSI detection.

cancer biology↗