Publications by authors named "Seiya Oura"
An inducible model of human post-implantation development derived from primed and naive stem cells.
Cell Stem Cell
August 2025
Early post-implantation human development is poorly understood due to limited access to natural embryos. Integrated stem cell-based embryo models (SCBEMs) offer an alternative, but current models face challenges in reproducibility, efficiency, and genomic stability. Here, we developed inducible SCBEMs (iSCBEMs) by combining primed human pluripotent stem cells (hPSCs) with transgene-induced extraembryonic cells derived from naive hPSCs.
View Article and Find Full Text PDFHuman pluripotent stem cells (hPSCs) exist in at least two distinct states of pluripotency: naïve and primed. While naïve hPSCs possess the unique ability to generate blastocyst-like structures, they are often genetically and epigenetically unstable, which compromises the quality and developmental potential of naïve hPSC-derived blastoids. This protocol presents an optimized human blastoid protocol through a transient resetting method that converts primed hPSCs into a naïve-like state, addressing the stability issues associated with long-term naïve hPSC maintenance.
View Article and Find Full Text PDFMitochondrial abundance and genome are crucial for cellular function, with disruptions often associated with disease. However, methods to modulate these parameters for direct functional dissection remain limited. Here, we eliminate mitochondria from pluripotent stem cells (PSCs) by enforced mitophagy and show that PSCs survived for several days in culture without mitochondria.
View Article and Find Full Text PDFPerturb-seq is a powerful approach to systematically assess how genes and enhancers impact the molecular and cellular pathways of development and disease. However, technical challenges have limited its application in stem cell-based systems. Here, we benchmarked Perturb-seq across multiple CRISPRi modalities, on diverse genomic targets, in multiple human pluripotent stem cells, during directed differentiation to multiple lineages, and across multiple sgRNA delivery systems.
View Article and Find Full Text PDFBackground: Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly.
View Article and Find Full Text PDFIncompatibility in cell adhesion constitutes a barrier to interspecies chimerism.
Cell Stem Cell
October 2024
Article Synopsis
- * A major challenge identified is the poor adhesion of human pluripotent stem cells (PSCs) to animal PSCs, which hinders the creation of effective chimeras.
- * To address this, researchers developed a synthetic biology technique that uses nanobody-antigen pairs to boost cell adhesion, leading to better integration of human PSCs in mouse embryos and improving understanding of cell interactions during early development.
Article Synopsis
- The sperm flagellar axoneme structure is crucial for sperm motility and is highly conserved across different species, aiding in fertilization.
- Mycbpap is primarily expressed in mouse and human testes and is vital for male fertility; its absence disrupts docking between the centrosome and nuclear envelope, causing defects in flagellar development.
- Research on transgenic mice showed that restoring MYCBPAP can recover fertility, and further studies revealed key protein interactions that highlight MYCBPAP’s role in regulating sperm tail formation and centrosome functions.
Multiple genes in the Pate5-13 genomic region contribute to ADAM3 processing†.
Biol Reprod
April 2024
Article Synopsis
- * A study used CRISPR/Cas9 to create knockout mouse models to investigate the importance of Pate family genes and related protein-coding genes in male fertility.
- * Results revealed that male mice lacking certain combinations of these genes showed reduced fertility due to lower levels of a key protein, ADAM3, and issues with sperm migration, indicating the collaborative function of these genes in promoting fertility.
Article Synopsis
- Recent advancements in creating human blastoids from naive pluripotent stem cells have improved the efficiency and quantity of these models for studying early human development and implantation.
- The new protocol allowed researchers to conduct proteomics analysis, revealing specific phosphosite signatures important for the signaling processes in human blastoids.
- Additionally, findings indicated that endometrial stromal cells support trophoblast cell survival and growth, while single-cell RNA sequencing helped identify similarities in gene expression between blastoids and blastocysts.
Article Synopsis
- Scientists have created in vitro stem cell models that mimic human gastrulation but previously lacked extraembryonic cells necessary for full embryonic development.
- A new method has been developed to encourage human extended pluripotent stem cells to self-organize into structures called peri-gastruloids, which include both embryonic and extraembryonic tissues.
- Although these peri-gastruloids are not viable, they successfully replicate important stages of early human development and show similar gene expression patterns to real human cells, potentially aiding future research in regenerative medicine.
Article Synopsis
- - Early embryo development is crucial for determining an organism's health and traits, and stem cell lines have been used for years to study this process.
- - Advances in stem cell culture have led to the creation of complex 3D structures that resemble early embryos, called blastoids, representing a major breakthrough in research.
- - This mini-review explores recent advancements in stem cell-based embryo models, their future potential, and their impact on understanding early mammalian development.
Article Synopsis
- Mammalian sperm must mature in the epididymis after being produced in the testis to be fully functional.
- This maturation is influenced by lumicrine signalling, which involves signals from the testis promoting sperm differentiation in the epididymis, though the mechanisms were not well understood.
- A protein called NICOL is shown to be vital for this process; without it, male mice become sterile due to issues with sperm maturation, but fertility can be restored by expressing NICOL in testicular cells.
TSKS localizes to nuage in spermatids and regulates cytoplasmic elimination during spermiation.
Proc Natl Acad Sci U S A
March 2023
Article Synopsis
- - Sperm have a specific shape to help them swim and fertilize eggs, but to achieve this shape, excess cytoplasm must be removed from developing sperm, a process called spermiation, whose detailed mechanisms are not fully understood.
- - Two types of structures called nuage, specifically reticulated body (RB) and chromatoid body remnant (CR), are found in sperm cells, but their functions remain unclear; however, new research shows they play a role in male fertility.
- - Researchers used CRISPR technology to remove a gene called TSKS in mice, revealing that TSKS is crucial for forming RB and CR; without it, excess cytoplasm remains in the sperm, leading to cell
Purpose: Microscopic testicular sperm extraction is the most effective treatment for NOA, but the sperm retrieval rate is low and depends on testicular maturity. However, there are limited useful tests to assess testicular maturity. Chemical exchange saturation transfer (CEST) imaging is a new magnetic resonance imaging (MRI) technique that can image the distribution of trace substances in vivo.
View Article and Find Full Text PDFBackground: TSN (translin), also called testis brain RNA-binding protein, binds to TSNAX (translin-associated factor X) and is suggested to play diverse roles, such as RNA metabolism and DNA damage response. TSNAXIP1 (Translin-associated factor X-interacting protein 1) was identified as a TSNAX-interacting protein using a yeast two-hybrid system, but its function in vivo was unknown.
Objective: To reveal the function of TSNAXIP1 in vivo in mice.
Characterization of protein-protein interactions (PPI) is a key to understanding the functions of proteins of interest. Recently developed proximity-dependent biotin identification (BioID) has been actively investigated as an alternative PPI mapping method because of its usefulness in uncovering transient PPI. Here, as an example of proximity labeling proteomics application in the testis, we generated two transgenic mouse lines expressing two biotin ligases (BioID2 or TurboID) fused with TESMIN, which translocates from the cytosol to the nucleus during meiotic progression and is required for reproduction.
View Article and Find Full Text PDFArticle Synopsis
- Meiosis is a crucial process in germ cell development that involves various molecular events, and understanding these is key to learning how meiosis works.
- Researchers identified TRIM41, an E3 ubiquitin ligase, as a vital factor for proper meiosis and male fertility, as its absence leads to issues like SYCP3 overloading on the X chromosome in knockout mice.
- The study indicates that TRIM41 plays a role in regulating protein dynamics on chromosome axes during meiosis, as shown by the behavior of mutant TRIM41 that lacks the RING domain necessary for its E3 activity.
Article Synopsis
- - The study examines the role of DCST1 and DCST2 proteins in sperm for fertilizing eggs in mice and zebrafish, showing they are critical for successful fertilization.
- - Mouse and zebrafish sperm lacking either DCST1 or DCST2 can perform initial sperm functions but ultimately fail to fuse with the egg, leading to infertility in males.
- - The proteins DCST1 and DCST2 are shown to interact and depend on each other, underscoring their importance as conserved elements in male fertility across different vertebrate species.
Article Synopsis
- The acrosome is a crucial organelle in sperm cells, playing a key role in reproduction, but the exact molecular processes behind its development are not fully understood.
- Research focused on two testis-enriched proteins, FAM71F1 and FAM71F2, showed that FAM71F1 is vital for male fertility, as mutant mice lacking this protein exhibited abnormal acrosome formation.
- Findings suggest that FAM71F1 interacts with RAB2A and RAB2B proteins to regulate vesicle trafficking, preventing excess movement of vesicles during acrosome development.
SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice.
Proc Natl Acad Sci U S A
August 2021
Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because sperm calcineurin has been proposed as a target for reversible male contraceptives, identifying proteins that interact with sperm calcineurin widens the choice for developing specific inhibitors.
View Article and Find Full Text PDFArticle Synopsis
- The CRISPR/Cas9 system, particularly the Streptococcus pyogenes Cas9 (WT-SpCas9), is important in gene therapy but limited by its requirement for a specific PAM sequence (NGG) to recognize target genes.
- Researchers developed an engineered Cas9 variant called SpCas9-NG, which can target broader PAM sequences (NGN), allowing for easier access to various gene mutations.
- In a study involving Huntington's disease, SpCas9-NG successfully repaired expanded CAG repeats in stem cells, demonstrating recovery of phenotypic issues in both neurons and derived animals, indicating its potential for targeting hard-to-reach mutations.
Article Synopsis
- - Meiosis is a complex cell division process, and researchers identified the gene Kctd19 as crucial for this process in male mice using CRISPR/Cas9 to screen genes involved in reproduction.
- - Kctd19 deficiency didn't hinder early meiosis stages like synapsis but did cause spermatocytes to undergo apoptosis during the transition from metaphase to anaphase.
- - The study also found that KCTD19 interacts with proteins ZFP541 and HDAC1, with both KCTD19 and ZFP541 being essential for normal meiosis, specifically in preventing DNA damage in spermatocytes.
ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility.
Proc Natl Acad Sci U S A
February 2021
Article Synopsis
- The study investigates the role of the protein ARMC12 in the formation of the mitochondrial sheath in mammalian sperm, which is crucial for sperm motility.
- By creating various genetically modified mouse models, the researchers found that the absence of ARMC12 leads to abnormal mitochondrial coiling and male sterility due to failed mitochondrial elongation during sperm development.
- The findings suggest that ARMC12 functions as an adherence factor that interacts with several mitochondrial proteins, highlighting its importance in maintaining proper mitochondrial dynamics essential for sperm function.
Article Synopsis
- The flagellum is crucial for sperm movement and fertilization, with the axoneme being its core structure made of microtubules and various protein complexes.
- Disruptions in the assembly of the axoneme components lead to fertility issues, and the gene Cfap97d1 is shown to be vital for proper sperm motility and male fertility.
- Knockout studies in mice reveal that loss of Cfap97d1 results in impaired sperm movement and structural abnormalities in the flagellum, significantly affecting fertility outcomes in in vitro fertilization experiments.
Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood.
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