Biology subjects

Toyota, T.

Publications and source records attributed to Toyota, T..

3 recordsLinked to original sources

bioRxiv2025

Generation of iPSC-derived CD4+ Th1 cells enhancing chimeric antigen receptor-T cell cytotoxicity

CD4+ T cells are anticipated to enhance the overall immune response, including the anti-tumor activity of chimeric antigen receptor (CAR)-T cell therapy. In the past, we established a culture system to generate CD8+ T cells from iPS cells (iPSCs); however, it was challenging to generate CD4+ T cells. Drawing inspiration from the observation that adult T cell leukemia (ATL) cells are consistently CD4+ and possess Treg characteristics, we successfully generated CD4+ Treg cells by reprogramming ATL cells into iPSCs and then differentiating them into T cells. Gene expression analysis of this generation system suggested that RUNX3 serves as a key regulator in T cell differentiation within the ex vivo generation system. By knocking out RUNX3, we demonstrated the generation of antigen-specific CD4+ Th1 cells via the iPSC route, thereby enhancing the activity of CD8+ CAR-T cells against GD2-expressing lymphoma. These technologies hold significant promise for contributing to "off-the-shelf" immunotherapies against malignant tumors, including solid tumors.

immunology↗

bioRxiv2020

Role of an atypical cadherin gene, Cdh23 in prepulse inhibition and its implication in schizophrenia

We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from an analysis of F2 mice from inbred strains with high (C57BL/6N; B6) and low (C3H/HeN; C3H) PPI levels. Here, we reanalyzed the previously reported QTLs with increased marker density. The highest LOD score (26.66) peaked at a synonymous coding and splice-site variant, c.753G>A (rs257098870), in the Cdh23 gene on chromosome 10; the c.753G (C3H) allele showed a PPI-lowering effect. Bayesian multiple QTL mapping also supported the same variant with a posterior probability of 1. Thus, we engineered the c.753G (C3H) allele into the B6 genetic background, which led to dampened PPI. We also revealed an e-QTL (expression-QTL) effect imparted by the c.753G>A variant for the Cdh23 expression in the brain. In a human study, a homologous variant (c.753G>A; rs769896655) in CDH23 showed a nominally significant enrichment in individuals with schizophrenia. We also identified multiple potentially deleterious CDH23 variants in individuals with schizophrenia. Collectively, the present study reveals a PPI-regulating Cdh23 variant and a possible contribution of CDH23 to schizophrenia susceptibility.

genetics↗

bioRxiv2018

Robust detection of tandem repeat expansions from long DNA reads

Tandemly repeated sequences are highly mutable and variable features of genomes. Tandem repeat expansions are responsible for a growing list of human diseases, even though it is hard to determine tandem repeat sequences with current DNA sequencing technology. Recent long-read technologies are promising, because the DNA reads are often longer than the repetitive regions, but are hampered by high error rates. Here, we report robust detection of human repeat expansions from careful alignments of long (PacBio and nanopore) reads to a reference genome. Our method (tandem-genotypes) is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we can prioritize pathological expansions within the top 10 out of 700000 tandem repeats in the genome. This may help to elucidate the many genetic diseases whose causes remain unknown.

genetics↗