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Enomoto, T.

Publications and source records attributed to Enomoto, T..

3 recordsLinked to original sources

Glucosinolate catabolism maintains glucosinolate profiles and transport in sulfur-starved Arabidopsis

Glucosinolates (GSL) are sulfur (S)-rich specialized metabolites produced by plants of the Brassicales order. Our previous study found that in Arabidopsis seedlings, S deficiency (-S) promoted GSL catabolism by activating two {beta}-glucosidases (BGLU), BGLU28 and BGLU30. The induced GSL catabolism was a survival strategy for seedlings grown under -S, because S released from GSL was reincorporated into primary S metabolites which are essential for plant growth. However, as GSL profile in plants vary among growth stages and organs, we set out to test a potential contribution of BGLU28/30-dependent GSL catabolism at the reproductive growth stage. Thus, in this study, we assessed growth, metabolic, and transcriptional phenotypes of mature bglu28/30 double mutants grown under different S conditions. Our results showed that compared to wild-type plants grown under -S, mature bglu28/30 mutants displayed impaired growth and accumulated increased levels of GSL in their mature seeds, siliques, flowers, and rosette leaves of before bolting plants. In contrast, the levels of primary S-containing metabolites, glutathione and cysteine, were decreased in mature seeds. Furthermore, the transport of GSL from rosette leaves to the reproductive organs was stimulated in the bglu28/30 mutants under -S. Transcriptome analysis revealed that genes related to other biological processes, such as phytohormone signaling and plant response to heat, responded differentially to -S in the bglu28/30 mutants. Altogether, these findings broadened our understanding of the roles of BGLU28/30-dependent GSL catabolism in plant adaptation to nutrient stress. One-sentence summaryDisruption of glucosinolate catabolic genes, BGLU28 and BGLU30, in sulfur-starved mature Arabidopsis impaired growth, affected glucosinolate distribution, and altered transcriptional profiles.

plant biology↗

MCM10 compensates for Myc-induced DNA replication stress in breast cancer stem-like cells

Cancer stem-like cells (CSCs) are responsible for the drug resistance of tumors and recurrence while they experience DNA replication stress. However, the underlying mechanisms that cause DNA replication stress in CSCs and how they compensate for this stress remain unclear. Here we provide evidence that upregulated c-Myc expression induces stronger DNA replication stress in patient-derived breast CSCs than in differentiated cancer cells. Our results suggest critical roles for mini-chromosome maintenance protein 10 (MCM10), which is a firing (activating) factor of the DNA replication origins, to compensate for the DNA replication stress. Expression levels of MCM10 are upregulated in CSCs and maintained by c-Myc. c-Myc-dependent collisions may take place between RNA transcription and DNA replication machinery in nuclei, thereby causing DNA replication stress. MCM10 may activate dormant replication origins close to the collisions to ensure replication progression. Moreover, patient-derived breast CSCs were dependent on MCM10 for their maintenance even after enrichment for CSCs that were resistant to paclitaxel, the standard chemotherapeutic agent. In addition, MCM10 depletion decreased the growth of cancer cells but not normal cells. Therefore, MCM10 is likely to robustly compensate for DNA replication stress and facilitate genome duplication in the S-phase in cancer cells, which is more pronounced in CSCs. We provide a preclinical rationale to target the c-Myc-MCM10 axis to prevent drug resistance and recurrence.

cancer biology↗

Three-dimensional understanding of the morphological complexity of the human uterine endometrium

SummaryThe histological basis of the human uterine endometrium has been established by 2D observation. However, the fundamental morphology of endometrial glands is not sufficiently understood because these glands have complicated winding and branching patterns. To construct a big picture of endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our 3D immunohistochemistry and 3D layer analyses revealed that endometrial glands formed a plexus network in the stratum basalis, similar to the rhizome of grass. We then extended our method to assess the 3D morphology of adenomyosis, a representative “endometrium-related disease”, and observed 3D morphological features including direct invasion of endometrial glands into the myometrium and an ant colony-like network of ectopic endometrial glands within the myometrium. Thus, 3D analysis of the human endometrium and endometrium-related diseases will be a promising approach to better understand the pathologic physiology of the human endometrium.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗