Biology subjects

Nakanishi, T.

Publications and source records attributed to Nakanishi, T..

4 recordsLinked to original sources

bioRxiv2026

Iro-C/IRX creates anti-cancerized epithelial field against IL-6-dependent malignant tumorigenesis

Some epithelial regions appear intrinsically resistant to malignancy, yet how such anti-cancerized fields are established remains elusive. Here, we show in Drosophila that Iroquois Complex (Iro-C), a group of transcriptional repressors specifically expressed in the notum region of the wing imaginal epithelium, creates anti-cancerized field against malignant tumorigenesis. Clones of cells with Ras activation and cell polarity defect (RasV12/scrib-/-) develop into malignant tumors in the pouch and hinge regions of the wing disc, yet they failed to overgrow in the notum. Mechanistically, intrinsic Iro-C expression in the notum represses upd/IL-6 transcription, thereby preventing JAK-STAT activation essential for driving malignant growth. Forced expression of Upd/IL-6 converted the notum into tumor-prone field, whereas forced expression of Iro-C in the pouch and hinge abolished their RasV12/scrib-/- tumorigenesis. Our findings provide a mechanistic explanation for how some epithelial regions, such as distal segments of the kidney, where Iro-C/IRX1 is specifically expressed, exhibit resistance to cancer development, and offer a novel therapeutic strategy against IL-6-dependent cancers.

cancer biology↗

bioRxiv2024

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients

Genome-wide association studies performed in patients with coronavirus disease 2019 (COVID-19) have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. However, the underlying cis-regulatory genetic factors that contribute to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we used single-cell RNA-sequencing to quantify genetic contributions to cis-regulatory variation in 361,119 peripheral blood mononuclear cells across 63 COVID-19 patients during acute infection, 39 samples collected in the convalescent phase, and 106 healthy controls. Expression quantitative trait loci (eQTL) mapping across cell types within each disease state group revealed thousands of cis-associated variants, of which hundreds were detected exclusively in immune cells derived from acute COVID-19 patients. Patient-specific genetic effects dissipated as infection resolved, suggesting that distinct gene regulatory networks are at play in the active infection state. Further, 17.2% of tested loci demonstrated significant cell state interactions with genotype, with pathways related to interferon responses and oxidative phosphorylation showing pronounced cell state-dependent variation, predominantly in CD14+ monocytes. Overall, we estimate that 25.6% of tested genes exhibit gene-environment interaction effects, highlighting the importance of environmental modifiers in the transcriptional regulation of the immune response to SARS-CoV-2. Our findings underscore the importance of expanding the study of regulatory variation to relevant cell types and disease contexts and argue for the existence of extensive gene-environment effects among patients responding to an infection.

genomics↗

bioRxiv2023

Size-Correlated Polymorphisms in Phyllotaxis-Like Periodic and Symmetric Tentacle Arrangements in Hydrozoan Polyps

IntroductionPeriodic organ arrangements occur during growth and development and are widespread in animals and plants. In bilaterian animals, the organs can be interpreted as being periodically arranged along the two-dimensional space and defined by two body axes; on the other hand, in radially symmetrical animals and plants, organs are arranged in the three-dimensional space around the body axis and around plant stems, respectively. The principles of periodic organ arrangement have primarily been investigated in bilaterians; however, studies on this phenomenon in radially symmetrical animals are scarce. MethodsIn the present study, we combined live imaging, quantitative analysis, and mathematical modeling to elucidate periodic organ arrangement in a radially symmetrical animal, Coryne uchidai (Cnidaria, Hydrozoa). ResultsThe polyps of C. uchidai simultaneously formed multiple tentacles to establish a regularly angled, ring-like arrangement with radial symmetry. Multiple rings periodically appeared throughout the body and mostly maintained symmetry. Furthermore, we observed polymorphisms in symmetry type, including tri-, tetra-, and pentaradial symmetries, as individual variations. Notably, the types of radial symmetry were positively correlated with polyp diameter, with a larger diameter in pentaradial polyps than in tetra- and triradial ones. Our mathematical model suggested the selection of size-correlated radial symmetry based on the activation-inhibition and positional information from the mouth of tentacle initiation. DiscussionOur established quantification methods and mathematical model for tentacle arrangements are applicable to other radially symmetrical animals, and will reveal the widespread association between size-correlated symmetry and periodic arrangement principles.

developmental biology↗

bioRxiv2022

Formation Of Small-World Network Containing Module Networks In Globally And Locally Coupled Map System With Changes In Global Connection With Time Delay Effects

In this study, we performed comprehensive morphological investigations of spontaneously formed network structures among elements in coupled map systems involving global connections that change depending on the synchronicity of states of elements and spatially local connections. The model formed various hierarchical networks, some of which were classified as small-world networks containing multiple module networks, similar to the neural network of mammalian brains. Moreover, such complex networks were formed in wider parameter regions when the global connection to an element from the other element was strengthened by the synchronization between the present and past states of the former and latter elements, respectively. This study suggests that the time delay effects for connection changed among elements and local interactions promoted the self-organization of small-world networks containing module networks, such as neural networks; neural networks contain them as spike-timing-dependent plasticity and inter-neuron interaction through glial cells.

biophysics↗