Biology subjects

Taniguchi, K.

Publications and source records attributed to Taniguchi, K..

10 recordsLinked to original sources

bioRxiv2026

Cytomegalovirus Infection in Human Cortical Organoids Induces Unique Developmental and Viral Substates

Human Cytomegalovirus (HCMV) is a ubiquitous {beta}-herpesvirus with exposure resulting in a life-long infection. Severe HCMV disease can occur in conditions of insufficient immunity, and this includes congenital infection. Infection of the developing brain can cause severe birth defects including microcephaly and sensorineural hearing loss. Also, increasing evidence suggests the contribution of HCMV infection in adult CNS diseases. Studying HCMV replication and its impact on CNS is restricted by host tropism and anatomy. In these studies, we define the impact of infection on healthy iPSC-derived cortical organoids using single cell RNA sequencing. We uncovered 16 cell type clusters in uninfected tissues using the Human Neural Organoid Cell Atlas. Following infection by HCMV expressing GFP, several clusters were altered in both GFP-positive and GFP-negative populations, including the likely transition of the Glutamatergic/GABAergic Neuron cluster into a CMV-Infected Cell cluster. Expressions of viral genes varied between cells and cell types, requiring us to introduce a TC (temporal class) indexing score to account for varying stages of infection. This analysis in conjunction with machine learning approaches revealed cells that are likely producing de novo HCMV along with several viral sub-states. Several viral sub-states had significant enrichments of genes involved in epithelial-to-mesenchymal (EMT) transition, including expression of EpCAM. We independently verified HCMV-induction of EpCAM protein expression in cortical organoids and glutamatergic neurons. In summary, our studies reveal unique features of HCMV infection of cortical organoid tissues, including varying viral sub-states and tropisms, and introduced new approaches to analyze these multi-dimensional complex data sets.

microbiology↗

bioRxiv2026

High resolution spatial transcriptomic and proteomic profiling of early primate gastrulation in utero

Early gastrulation represents a key stage in which several embryonic and extra-embryonic lineages are formed in the primitive streak to support embryonic development. However, very little is known about lineage specification events in the early primate gastrula. To gain molecular insights into mechanisms that organize this stage of primate development, we performed high-resolution spatial transcript and protein expression profiling of five sagittal sections from a cynomolgus macaque embryo at Carnegie Stage 6b, an early gastrulation stage. We established a molecular map of six major cell populations: the epiblast, primitive streak, amnion, endoderm, mesoderm, and primordial germ cells. We also uncovered a variety of lineage subtypes, as well as important signaling and transcriptional networks. In particular, we show that canonical WNT signaling is a driver of amnion fate progression. Together, this study provides a unique multiomic resource of an early primate gastrula with complete spatial information for future investigations.

developmental biology↗

bioRxiv2025

Cellular fitness is determined by ribosomal protein S12-mediated release of a truncated Xrp1

Multicellular tissues require continuous optimization to maintain their structure and function by actively eliminating viable, yet unfit cells via a mechanism known as cell competition. During this process, unfit loser cells commonly upregulate the C/EBP family transcription factor Xrp1, which causes their elimination, indicating that intracellular Xrp1 levels determine cellular fitness. However, despite its central role, the mechanism by which Xrp1 is upregulated in unfit cells remains unknown. Here, we show that Xrp1 is upregulated through a previously unrecognized post-transcriptional regulatory mechanism mediated by the ribosomal protein S12 (RpS12). Surprisingly, Xrp1 mRNA is abundantly expressed even in wild-type cells, yet it is not translated. This is due to an upstream open reading frame (uORF) located in the 5UTR of the initial coding exon of Xrp1 mRNA, which inhibits the translation of the main Xrp1 ORF. Intriguingly, in unfit cells, RpS12 causes splicing-mediated skipping of this initial exon, leading to the use of an alternate start codon that generates a short isoform of Xrp1 protein, causing cell death. Notably, protein structural analysis reveals that RpS12 is highly homologous to that of a spliceosomal component SNU13, suggesting the role of RpS12 in directly regulating alternative splicing of Xrp1 mRNA. Our findings thus provide not only a mechanistic insights into how cellular fitness is determined but also how tissue optimization is achieved.

cell biology↗

bioRxiv2025

The endo-lysosomal system drives lumen formation in a human epiblast model

The formation of a central lumen in the epiblast is a critical step that occurs during implantation in the human embryo. Lumen formation is accompanied by highly dynamic and complex cargo trafficking in the endo-lysosomal system. However, our understanding of key players and machineries that control this critical trafficking process remains incomplete in the context of epiblast development. Here, we explored endo-lysosomal dynamics that are associated with the generation of the apicosome, the earliest stage of lumen formation in a model of human epiblast development based on human pluripotent stem cells. We uncovered a hybrid early/late endosome compartment as well as a previously unrecognized dynamics of late endosome and lysosome compartments in trafficking podocalyxin (PODXL), a sialomucin glycoprotein that helps to establish and maintain the open lumen, during apicosome formation. To gain molecular insight into these unique hybrid endosome and late endosome/lysosome machineries in PODXL traffic, we used APEX2-based spatial proteomics to identify PODXL-proximity partners during apicosome formation, and identified RAB35, a Rab small GTPase known to control PODXL traffic as well as early and late endosome dynamics, as a key player in controlling apicosome formation. Our results suggest that RAB35 limits excess apicosome formation by promoting the early to late endosome transition as well as lysosome formation, which help to reduce PODXL to a level necessary for single apicosome formation. Overall, this study reveals novel endo-lysosomal mechanisms that contribute to apical membrane morphogenesis in a human model of epiblast formation.

developmental biology↗

bioRxiv2024

Bioinformatic evaluation of the potential oral-gut translocation of periodontal pathogens in patients with colorectal polyps

ObjectiveThis study aimed to characterize the profiles of the oral and gut microbiota of patients with colorectal polyps using 16S rRNA gene sequencing and bioinformatic approaches. BackgroundPrevious studies have shown microbial translocation from the oral cavity to the gut, implying pathogenic impacts on gastroesophageal disease, including colorectal cancer (CRC). However, its details remain unclear. MethodsTwenty patients scheduled for endoscopic colorectal polypectomy were enrolled in this study. Oral samples (saliva and subgingival dental plaque) and intestinal samples (feces and swab of intestinal mucosa) were collected during preoperative and 6-month-postoperative reassessment periods. After sequencing the V3-V4 region of the bacterial 16S rRNA gene, several bioinformatic analyses (bacterial composition, diversity, core microbiome, and shared ASV) were performed on pre- and postoperative samples for each subject. ResultsThe bacterial composition was dominated by Bacteroides, Streptococcus, Fusobacterium, Veillonella, and Prevotella_7 in all four samples. Beta diversity analysis using weighted UniFrac distance distinctly segregated the samples between oral and intestinal environments in the principal coordinate analysis plot. Core microbiome analysis revealed that Streptococcus and Porphyromonas were dominantly shared in intra-oral environments. Additionally, alongside Streptococcus, periodontitis-related bacteria, such as Veillonella, Fusobacterium, Porphyromonas, Prevotella_7, Haemophilus, and Prevotella, were identified as shared genera between oral and intestinal environments. Finally, shared ASV analysis demonstrated that Streptococcus was shared in the oral and intestinal environments of most patients, while periodontal pathogens were shared in some patients. ConclusionsThe core microbiome and shared ASV analyses revealed that several genes are shared between oral and intestinal environments in patients with colorectal polyps, indicating the oral-gut translocation of periodontitis-related bacteria. Further large-scale studies are needed to elucidate their involvement in CRC.

bioinformatics↗

bioRxiv2023

Identification of amnion progenitor-like cells at the amnion-epiblast boundary in the primate peri-gastrula

Amniogenesis is triggered in a collection of pluripotent epiblast cells as the human embryo implants. To gain insights into the critical but poorly understood transcriptional machinery governing amnion fate determination, we examined the evolving transcriptome of a developing human pluripotent stem cell-derived amnion model at the single cell level. This analysis revealed several continuous amniotic fate progressing states with state-specific markers, which include a previously unrecognized CLDN10+ amnion progenitor state. Strikingly, we found that expression of CLDN10 is restricted to the amnion-epiblast boundary region in the human post-implantation amniotic sac model as well as in a peri-gastrula cynomolgus macaque embryo, bolstering the growing notion that, at this stage, the amnion-epiblast boundary is a site of active amniogenesis. Bioinformatic analysis of published primate peri-gastrula single cell sequencing data further confirmed that CLDN10 is expressed in cells progressing to amnion. Additionally, our loss of function analysis shows that CLDN10 promotes amniotic but suppresses primordial germ cell-like fate. Overall, this study presents a comprehensive amniogenic single cell transcriptomic resource and identifies a previously unrecognized CLDN10+ amnion progenitor population at the amnion-epiblast boundary of the primate peri-gastrula.

developmental biology↗

bioRxiv2023

Temporally resolved early BMP-driven transcriptional cascade during human amnion specification

Amniogenesis, a process critical for continuation of healthy pregnancy, is triggered in a collection of pluripotent epiblast cells as the human embryo implants. Previous studies have established that BMP signaling is a major driver of this lineage specifying process, but the downstream BMP-dependent transcriptional networks that lead to successful amniogenesis remain to be identified. This is, in part, due to the current lack of a robust and reproducible model system that enables mechanistic investigations exclusively into amniogenesis. Here, we developed an improved model of early amnion specification, using a human pluripotent stem cell-based platform in which the activation of BMP signaling is controlled and synchronous. Uniform amniogenesis is seen within 48 hours after BMP activation, and the resulting cells share transcriptomic characteristics with amnion cells of a gastrulating human embryo. Using detailed time-course transcriptomic analyses, we established a previously uncharacterized BMP-dependent amniotic transcriptional cascade, and identified markers that represent five distinct stages of amnion fate specification; the expression of selected markers was validated in early post-implantation macaque embryos. Moreover, a cohort of factors that could potentially control specific stages of amniogenesis was identified, including the transcription factor TFAP2A. Functionally, we determined that, once amniogenesis is triggered by the BMP pathway, TFAP2A controls the progression of amniogenesis. This work presents a temporally resolved transcriptomic resource for several previously uncharacterized amniogenesis states and demonstrates a critical intermediate role for TFAP2A during amnion fate specification.

developmental biology↗

bioRxiv2022

The Drosophila AWP1 ortholog Doctor No regulates JAK/STAT signaling for left-right asymmetry in the gut by promoting receptor endocytosis

Many internal Drosophila organs show stereotypical left-right (LR) asymmetry, for which the underlying mechanisms remain elusive. Here, we identified an evolutionarily conserved ubiquitin-binding protein, AWP1/Doctor no (Drn), as a novel factor required for the LR asymmetry of the embryonic anterior gut in Drosophila. We showed that drn is essential in the circular visceral muscle cells of the midgut for JAK/STAT signaling, which contributes to the first known cue for anterior gut lateralization via LR-asymmetric nuclear rearrangement. Embryos homozygous for drn and lacking its maternal contribution showed phenotypes similar to that of depleted JAK/STAT signaling, suggesting that Drn is a general component of JAK/STAT signaling. The absence of Drn resulted in the specific accumulation of Domeless (Dome), the receptor of JAK/STAT signaling, in intracellular compartments. Thus, Drn is required for the endocytic trafficking of Dome, which is subsequently degraded in lysosomes. Our results suggest that the endocytosis of Dome is a critical step in activating JAK/STAT signaling. The roles of AWP1/Drn in activating JAK/STAT signaling and in LR-asymmetric development may be conserved in various organisms. Summary StatementDr. No, a Drosophila ortholog of AWP1, activates JAK/STAT signaling via Dome receptor endocytosis in a crucial step for left-right asymmetry in the developing gut.

developmental biology↗

bioRxiv2021

A chromosome-level genome sequence of a model chrysanthemum: evolution and 1 reference for hexaploid cultivated chrysanthemum

Chrysanthemums are one of the most industrially important cut flowers worldwide. However, their segmental allopolyploidy and self-incompatibility have prevented the application of genetic analysis and modern breeding strategies. We thus developed a model strain, Gojo-0 (Chrysanthemum seticuspe), which is a diploid and self-compatible pure line. Here, we present the 3.05 Gb chromosome-level reference genome sequence, which covered 97% of the C. seticuspe genome. The genome contained more than 80% interspread repeats, of which retrotransposons accounted for 72%. We identified recent segmental duplication and retrotransposon expansion in C. seticuspe, contributing to a relatively large genome size. Furthermore, we identified aretrotransposon, SbdRT, which was enriched in gene-dense genome regions and had experienced a very recent transposition burst. We also demonstrated that the chromosome-level genome sequence facilitates positional cloning in C. seticuspe. The genome sequence obtained here can greatly contribute as a reference for chrysanthemum in front-line breeding including genome editing.

plant biology↗

bioRxiv2020

Collection of 2429 constrained headshots of 277 volunteers for deep learning

Deep learning has rapidly been filtrating many aspects of human lives. In particular, image recognition by convolutional neural networks has inspired numerous studies in this area. Hardware and software technologies as well as large quantities of data have contributed to the drastic development of the field. However, the application of deep learning is often hindered by the need for big data and the laborious manual annotation thereof. To experience deep learning using the data compiled by us, we collected 2429 constrained headshot images of 277 volunteers. The collection of face photographs is challenging in terms of protecting personal information; we established an online procedure in which both the informed consent and image data could be obtained. We did not collect personal information, but issued agreement numbers to deal with withdrawal requests. Gender and smile labels were manually and subjectively annotated only from the appearances, and final labels were determined by majority among our team members. Rotated, trimmed, resolution-reduced, decolorized, and matrix-formed data were allowed to be publicly released. Moreover, simplified feature vectors for data sciences were released. We performed gender recognition by building convolutional neural networks based on the Inception V3 model with pre-trained ImageNet data to demonstrate the usefulness of our dataset.

animal behavior and cognition↗