Biology subjects

Tomoda, K.

Publications and source records attributed to Tomoda, K..

3 recordsLinked to original sources

bioRxiv2025

eIF4G2-Mediated Translation Initiation of Histone Modifiers Is Essential for Intestinal Stem Cell Maintenance and Differentiation

eIF4G2 (also known as NAT1, p97, or DAP5) is an evolutionally conserved protein homologous to the C-terminal two-thirds portion of eukaryotic translation initiation factor (eIF) 4G. Despite its abundant and ubiquitous expression, the physiological and pathological functions of eIF4G2 are poorly understood. Here, we show that acute loss of eIF4G2 in adult mice results in rapid weight loss with abnormalities in multiple organs, including impaired maintenance and differentiation of intestinal stem cells. Genome-wide ribosome profiling revealed that eIF4G2 is critical for the translation of key histone modification proteins involved in intestinal stemness. Our study underscores the importance of eIF4G2-mediated translation initiation in multicellular organisms.

cell biology↗

bioRxiv2020

Reprogramming Epiblast Stem Cells into Pre-Implantation Blastocyst Cell-like Cells

Recently, a new wave of synthetic embryo systems (SESs) have been established from cultured cells toward efficient and ethical embryonic development research. We recently reported our epiblast stem cell (EPISC) reprogramming SES that generates numerous blastocyst (BC)-like hemispheres (BCLH) with pluripotent and extraembryonic cell features detected microscopically. Here, we further explored the system over key time points with unprecedented single-cell RNA sequencing (scRNA-seq) analysis and revealed broad induction of the 2C-like reporter MERVL and RNA velocity diverging three major population regions with genetic expression resembling pluripotent epiblast (EPI), primitive endoderm (PE), and trophectoderm (TE). Enrichment of those three BC-like cell fates involved key regulons, zygotic genome activation (ZGA) related genes, specific RNA splicing, and select cells meaningfully distinguished critical regulons of model cells. This analysis confirms the induction of the extraembryonic cell populations during the reprogramming and we anticipate that our unique BCLH SES and rich data may uncover new facets of cell potency, improve developmental biology, and help biomedicine advance.

synthetic biology↗

bioRxiv2018

Implantation-Competent Blastocyst-Like Structures from Mouse Pluripotent Stem Cells

Soon after fertilization, the few totipotent cells of mammalian embryos diverge to form a structure called the blastocyst (BC). Although numerous types of cells, including germ cells and extended pluripotency stem cells, have been generated from pluripotent stem cells (PSCs) in-vitro, generating functional BCs only from PSCs has not yet been reported. Here we describe induced self-organizing 3D BC-like structures (iBCs) generated from mouse PSC culture in-vitro. Resembling natural BCs, iBCs have a blastocoel-like cavity and were formed with outer cells that are positive for trophectoderm lineage markers and with inner cells that are positive for pluripotency markers. iBCs transplanted to pseudopregnant mice uteruses implanted, induced decidualization, and exhibited growth and development before resorption, demonstrating that iBCs are implantation-competent. iBC production required the transcription factor Prdm14 and iBC precursor intermediates concomitantly activate the MERVL totipotency related cleavage stage reporter. Thus, our system may contribute to understanding molecular mechanisms underpinning totipotency, embryogenesis, and implantation.\n\nHIGHLIGHTS-Pluripotent cells self-organize blastocyst-like structures in defined conditions.\n-Structures have several extraembryonic and embryonic characteristics of blastocysts.\n-Structures can implant in the uterus and grow before resorption.\n-Totipotency is implicated concomitantly at loci that originate induced blastocysts.

developmental biology↗