Biology subjects

Harada, I.

Publications and source records attributed to Harada, I..

3 recordsLinked to original sources

bioRxiv2025

Multiple fertility restorer loci for cytoplasmic male sterility caused by orf137 in tomato

Cytoplasmic male sterility (CMS) in plants is caused by incompatibility between nuclear and cytoplasmic genetic information. Fertility can be restored through the action of fertility restoration (RF) genes, which are usually present in the nucleus. CMS lines of tomato (Solanum lycopersicum) have been developed from asymmetric cell fusions, in these lines, cultivated tomato served as a nuclear donor and its wild relative, S. acaule, as a cytoplasm donor. Although RF genes are present in wild relatives of tomato, no genetic or genomic information on the RF genes is yet available. This study reports an RF genetic locus, RF1, on chromosome 1 of S. pimpinellifolium LA1670 and S. lycopersicum var. cerasiforme LA1673 that was revealed by bulked segregant analysis and sequencing. An additional RF locus, RF2, was identified on chromosome 2 of LA1670. A transgenic approach identified two other candidate genes that also restored fertility. The genomic sequence of S. cheesmaniae LA0166 was assembled using high-fidelity, long-read sequencing technology. Sequence comparisons identified further candidate RF genes on chromosome 1 of S. cheesmaniae LA0166. These results suggested that multiple gene loci control the fertility restoration trait in wild relatives of tomato.

plant biology↗

bioRxiv2025

Inhibition of EMT driver PTK6 enhances anti-tumor immune responses against triple-negative breast cancer

The non-receptor tyrosine kinase PTK6 is expressed in 70% of triple negative breast cancers (TNBC) and is an oncogenic driver of epithelial-mesenchymal transition (EMT). EMT promotes metastasis and immune evasion of TNBC. Therefore, targeting EMT drivers could reverse these properties and lead to more favorable outcomes. Treatment of TNBC tumors with a small molecule inhibitor of PTK6 kinase (P21d) suppressed their growth in vivo. Tumor inhibition by P21d is dependent on an induced immune response because: 1) inhibition is observed in immunocompetent, but not immunodeficient, mice; 2) P21d increases tumor-infiltrating CD8+ T and NK cells and decreases immunosuppressive myeloid-derived suppressor cells; and 3) tumor inhibition by P21d is abrogated by co-treatment with NK or CD8+ T cell-depleting antibodies. These effects on tumor growth and cytotoxic TILs are phenocopied by the knockdown of tumoral PTK6 or SNAIL, which supports EMT inhibition as a mechanism for enhanced anti-tumor immune response. RNA sequencing (RNA-seq) profiling of P21d-treated tumors also revealed changes consistent with activation of the immune response and identified CXCL10 as a critical chemokine induced intratumorally by P21d that promotes recruitment of NK/CD8+ T cells to the tumor site, leading to tumor growth inhibition. Our study highlights the novel tumor immune microenvironmental functions of PTK6 with important consequences for tumor growth that could lead to new immunotherapeutic approaches for TNBC.

cancer biology↗

bioRxiv2021

Organelle genome assembly uncovers the dynamic genome reorganization and cytoplasmic male sterility associated genes in tomato.

To identify cytoplasmic male sterility (CMS)-associated genes in tomato, we determined the genome sequences of mitochondria and chloroplasts in three CMS tomato lines derived from independent asymmetric cell fusions, their nuclear and cytoplasmic donors, and male fertile weedy cultivated tomato and wild relatives. The structures of the CMS mitochondrial genomes were highly divergent from those of the nuclear and cytoplasmic donors, and genes of the donors were mixed up in these genomes. On the other hand, the structures of CMS chloroplast genomes were moderately conserved across the donors, but CMS chloroplast genes were unexpectedly likely derived from the nuclear donors. Comparative analysis of the structures and contents of organelle genes and transcriptome analysis identified three genes that were uniquely present in the CMS lines, but not in the donor or fertile lines. RNA sequencing analysis indicated that these three genes transcriptionally expressed in anther, two of which were also expressed in pollen. They could be potential candidates for CMS-associated genes. This study suggests that organelle reorganization mechanisms after cell fusion events differ between mitochondria and chloroplasts, and provides insight into the development of new F1 hybrid breeding programs employing the CMS system in tomato.

plant biology↗