Biology subjects

Mikami, T.

Publications and source records attributed to Mikami, T..

5 recordsLinked to original sources

bioRxiv2026

Personalized reference genome-based pipeline reveals comprehensive haplotype-resolved views of cancer genomes

Cancer genome analysis relies on standard human reference genomes, but detecting somatic alterations in highly repetitive or individual-specific regions remains challenging. We developed the Personalized Reference genome-based Cancer Genome Analysis Pipeline (PRCGAP, https://github.com/yos-sk/PRCGAP), to our knowledge, the first comprehensive pipeline integrating haplotype-resolved analyses of somatic point mutations, structural variants, copy number, and DNA methylation on personalized diploid reference genomes, with each variant phased and annotated by genomic features. We applied PRCGAP to eight tumor-normal cell line pairs and three newly collected pediatric B-cell acute lymphoblastic leukemia (B-ALL) clinical samples. PRCGAP recovered most standard reference-based variants (86.7-96.4% across variant types), validated by orthogonal short-read sequencing, while additionally detecting variants that standard references missed (23.4% of SNVs and 32.6% of SVs). Notably, PRCGAP uncovered variants in centromeric and telomeric regions, and somatic single-nucleotide variants were enriched in centromere dip regions, the putative kinetochore formation sites. Using PRCGAP outputs, we identified L1 retrotransposition source sites absent from standard references and showed that a B-ALL IGH::DUX4 fusion arose from a DUX4 pseudogene within an internal D4Z4 repeat unit, rather than the canonical full-length DUX4 gene. Within a single haplotype-resolved framework, PRCGAP opens regions of the cancer genome that are inaccessible to standard references.

bioinformatics↗

bioRxiv2026

Hmgb1 release kinetics shape its extracellular functions during regulated cell death

Danger-associated molecular patterns (DAMPs), such as high mobility group protein B1 (HMGB1), are released from dying cells, yet the kinetics and functional consequences of their release remain unclear. Using Hmgb1-mCherry transgenic mice and live-cell imaging, we visualize Hmgb1 and interleukin-1{beta} (IL-1{beta}) secretion at single-cell resolution. Hmgb1 exhibits two distinct release kinetics: short-duration completed within 1 min and long duration spanning several minutes. Mathematical modeling demonstrates that short-duration release generates substantially higher local Hmgb1 concentrations and steeper gradients near the dying cell than long-duration release. Such rapid release may enable one or a few dying cells to produce sufficient Hmgb1 to stimulate neighboring cells, consistent with its role as an alarmin. In vivo imaging of cisplatin-induced kidney injury reveals an inverse correlation between intracellular Hmgb1 levels and monocyte infiltration. Together, these findings suggest that Hmgb1 release kinetics shape its extracellular functions during regulated cell death.

cell biology↗

bioRxiv2022

A FRET biosensor, SMART, monitors necroptosis in renal tubular epithelial cells in a cisplatin-induced kidney injury model

Necroptosis is a regulated form of cell death involved in various pathological conditions, including ischemic reperfusion injuries, virus infections, and drug-induced tissue injuries. However, it is not fully understood when and where necroptosis occurs in vivo. We previously generated a Forster resonance energy transfer (FRET) biosensor, termed SMART (the sensor for MLKL activation based on FRET), which specifically monitored necroptosis in human and murine cell lines in vitro. Here, we generated transgenic (Tg) mice that expressed the SMART biosensor in various tissues. SMART monitored necroptosis, but not apoptosis or pyroptosis, in primary cells, including peritoneal macrophages and embryonic fibroblasts. Moreover, the FRET signal was elevated in renal tubular cells of cisplatin-treated SMART Tg mice compared to untreated SMART Tg mice. Together, SMART Tg mice may provide a valuable tool for monitoring necroptosis in different types of cells in vitro and in vivo.

cell biology↗

bioRxiv2020

The balancing act of Nipponites mirabilis (Nostoceratidae, Ammonoidea): managing hydrostatics during a complex ontogenetic trajectory

Nipponites is a heteromorph ammonoid with a complex and unique morphology that obscures its mode of life and ethology. The seemingly aberrant shell of this Late Cretaceous nostoceratid seems deleterious. However, hydrostatic simulations suggest that this morphology confers several advantages for exploiting a quasi-planktic mode of life. Virtual, 3D models of Nipponites mirabilis were used to compute various hydrostatic properties through 14 ontogenetic stages. At each stage, Nipponites had the capacity for neutral buoyancy and was not restricted to the seafloor. Throughout ontogeny, horizontally facing to upwardly facing soft body orientations were preferred. These orientations were aided by the obliquity of the shells ribs, which were parallel to former positions of the aperture during life. Static orientations were somewhat fixed, inferred by stability values that are slightly higher than extant Nautilus. The initial open-whorled, planispiral phase is well suited to horizontal backwards movement with little rocking. Nipponites then deviates from this coiling pattern with a series of alternating U-shaped bends in the shell. This modification allows for proficient rotation about the vertical axis, while possibly maintaining the option for horizontal backwards movement by redirecting its hyponome. These particular hydrostatic properties likely result in a tradeoff between hydrodynamic streamlining, suggesting that Nipponites assumed a low energy lifestyle of slowly pirouetting in search for planktic prey. Each computed hydrostatic property influences the others in some way, suggesting that Nipponites maintained a delicate hydrostatic balancing act throughout its ontogeny in order to facilitate this mode of life.

paleontology↗

bioRxiv2020

Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

Interleukin (IL)-11 is a member of the IL-6 family of cytokines and involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells appeared in the colon of three murine tumor models, and a murine acute colitis model. Il11ra1 or Il11 deletion attenuated the development of colitis-associated colorectal cancer. IL-11+ cells expressed fibroblast markers, and genes associated with cell proliferation and tissue repair. IL-11 induced STAT3 phosphorylation in colonic fibroblasts, suggesting the activation of IL-11+ fibroblasts. Analysis using the human cancer database revealed that genes enriched in IL-11+ fibroblasts were elevated in human colorectal cancer, and correlated with reduced disease-free survival. Together, our results suggested that tumor cells induced IL-11+ fibroblasts, and that a feed-forward loop between IL-11 and IL-11+ fibroblasts might contribute to tumor development.

cancer biology↗