Biology subjects

Sanaki, Y.

Publications and source records attributed to Sanaki, Y..

3 recordsLinked to original sources

bioRxiv2026

ISP Platform powered by Geneformer: Framework for Cross-Species, Sequential, and Multi-Gene In Silico Perturbation Screens with Application to iPS Cell State Transitions

In silico perturbation (ISP) enables virtual genetic screens, prioritizing candidate regulators before costly wet-lab experiments. However, applying foundation models requires programming expertise. Here, we present the ISP Platform, that automates ISP powered by Geneformer without code execution. The platform enables cross-species analyses by independently selecting input species and human or mouse Geneformer models. The platform also implements sequential multi-gene ISP, in which each perturbation chains from the cell state produced by the preceding step. Using induced pluripotent stem cell (iPSC) datasets, the platform successfully performed cross-species analysis of human and mouse single cell-RNA (scRNA)-seq data. Screening all 24 permutations of the Yamanaka factors identified an optimal overexpression sequence that produced the highest shift toward the pluripotent state. Genome-wide knockdown screens prioritized key pluripotency regulators but revealed an asymmetric cross-species concordance. The human model effectively captured mouse pluripotency programs, whereas applying the mouse model to human cells yielded predominantly translation-related terms. Furthermore, a targeted pairwise overexpression screen nominated candidate modulators of the primed-to-naive transition beyond the conventional NANOG and KLF2 benchmark. Together, the ISP Platform provides a unified, accessible framework for three dimensions of in silico perturbation (cross-species, sequential, and multi-gene) to guide focused experimental validation and reduce exploratory animal use.

bioinformatics↗

bioRxiv2025

EC-isHCR: a rapid method for in situ hybridization chain reaction in diverse animal samples

The in situ hybridization chain reaction (isHCR) visualizes RNA across multiple spatial scales, from organs to subcellular structures, in diverse samples. We previously proposed a rapid protocol, EC-isHCR, for Drosophila embryos and ovaries. Whether EC-isHCR retains the features of conventional isHCR, including wide-spatial-scale analyses in various samples, however, has remained unclear. Here, we show that EC-isHCR enables robust RNA detection in a broad range of samples, such as whole-mount fruit fly, parasitoid wasp, and aphid preparations; paraffin sections of trout; frozen mouse sections; and human cultured cells. Moreover, EC-isHCR enabled detection of subcellular RNA localization. EC-isHCR also visualized co-localization of RNA with phase-separated condensates in fruit fly embryos and detected the protrusion-enriched mRNA in HeLa cells. To broaden the applicability of EC-isHCR, we developed an automated probe design tool (https://github.com/ShuntaYorimoto/hcrkit). By combining this tool with EC-isHCR, we provide a fast and versatile framework to visualize mRNAs. This framework will help reduce the barrier to using fast isHCR and thereby facilitate research across diverse areas of the life sciences. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/696653v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1852584org.highwire.dtl.DTLVardef@621682org.highwire.dtl.DTLVardef@1b3bf5corg.highwire.dtl.DTLVardef@1d86841_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- EC-isHCR enables rapid acquisition of high-contrast images. - EC-isHCR preserves features of conventional isHCR, including versatile sample compatibility and high-resolution imaging. - An automated probe design tool was developed for EC-isHCR. - EC-isHCR/probe tool framework will help reduce the barrier to using fast isHCR.

bioengineering↗

bioRxiv2025

Xrp1 drives damage-induced cellular plasticity of enteroendocrine cells in the adult Drosophila midgut

Cellular plasticity, the ability of a differentiated cell to adopt another phenotypic identity, is restricted under basal conditions, but can be elicited upon damage to facilitate regeneration. Such damage-induced cellular plasticity restores homeostasis and prevents pathology, yet its underlying molecular basis remains largely unexplored. Here, we reported damage-induced cellular plasticity of secretory enteroendocrine cells (EEs) in the adult Drosophila midgut. We found that ionizing radiation enhanced EE plasticity such that it promoted EEs to dedifferentiate into ISCs and subsequently re-differentiate towards ECs. We identified that radiation induced the production of a stress-inducible transcription factor Xrp1 in EE lineages, and its upregulation was necessary for EE plasticity. Single-cell RNA sequencing of guts with EE-specific Xrp1 overexpression revealed ectopic expression of progenitor-specific genes in EEs, which was necessary for Xrp1 to drive EE plasticity. Our work provides a mechanistic framework for understanding cellular plasticity and suggests its potential role in damage-induced responses.

cell biology↗