A5067253013- CRISPR and Genetic Engineering
- Reproductive Biology and Fertility
- Pluripotent Stem Cells Research
- Sperm and Testicular Function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Epigenetics and DNA Methylation
- Renal and related cancers
- Animal Genetics and Reproduction
- Sexual Differentiation and Disorders
- Prenatal Screening and Diagnostics
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Down syndrome and intellectual disability research
- Reproductive Health and Technologies
- Pancreatic function and diabetes
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Virus-based gene therapy research
- Ovarian function and disorders
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Viral Infectious Diseases and Gene Expression in Insects
RIKEN BioResource Research Center
2015-2024
Tokyo University of Agriculture and Technology
2018-2024
University of Tsukuba
2022
Harvard University
2012-2018
Howard Hughes Medical Institute
2012-2018
Boston Children's Hospital
2014-2018
The University of Tokyo
2003-2013
Harvard Stem Cell Institute
2013
Swedish University of Agricultural Sciences
2004
Dankook University
2004
Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status, including histone modification. Although several play crucial roles in mammalian sex determination, how regulation contributes to this process remains unknown. We observed male-to-female reversal mice lacking H3K9 demethylase Jmjd1a found that regulates Y chromosome sex-determining Sry. directly positively controls Sry by regulating H3K9me2 marks. These studies...
Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because erroneous reprogramming the donor genome. Reprogramming errors appear to arise randomly, but nature nonrandom, SCNT-specific remains elusive. We found that Xist, a noncoding RNA inactivates one two X chromosomes in females, was ectopically expressed from active (Xa) chromosome cloned mouse embryos both sexes. Deletion Xist on Xa showed normal global gene expression and resulted about an eight-...
In mammals, the Y-linked sex-determining gene Sry cell-autonomously promotes Sertoli cell differentiation from bipotential supporting precursors through SRY-box containing 9 (Sox9), leading to testis formation. Without action, cells differentiate into granulosa cells, resulting in ovarian development. However, how acts spatiotemporally switch female male pathway is poorly understood. We created a novel transgenic mouse line bearing an inducible transgene under control of Hsp70.3 promoter....
Sox7, Sox17 and Sox18 constitute group F of the Sox family HMG box transcription factor genes. Dominant-negative mutations in underlie cardiovascular defects observed ragged mutant mice. By contrast, Sox18-/- mice are viable fertile, display no appreciable anomaly their vasculature, suggesting functional compensation by two other SoxF Here, we provide direct evidence for redundant function postnatal neovascularization generating Sox17+/--Sox18-/- double Whereas Sox17+/--Sox18+/- showed...
Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient. Most SCNT-generated embryos die after implantation because of unidentified, complex epigenetic errors in the process postimplantation embryonic development. Here we identify most upstream level dysfunction leading to impaired development clones using RNAi against Xist, a gene responsible for X chromosome inactivation (XCI). A prior injection Xist-specific siRNA into reconstructed oocytes efficiently corrected...
Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding (PCGs) disrupted. Tc1 is mosaic, compromising interpretation results. Here, we “clone” the 34 MB long arm (HSA21q) as artificial (MAC). Through multiple steps microcell-mediated transfer, created new Tc Tc(HSA21q;MAC)1Yakaz...
Significance Mammalian oocytes are surrounded by the zona pellucida, a glycoprotein coat that protects oocyte and embryo from mechanical damage during their preimplantation development within oviduct. Fertilizing spermatozoa must penetrate zona, but we do not know exact mechanisms underlying this process. Sperm proteases were thought to work as lysins, gene-knockout studies in mice did support assumption. In study, generated hamsters without acrosin, major acrosomal protease, examine its...
Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However, Dux-knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven an unknown factor(s). Here, we present multiple lines evidence the multicopy homeobox gene, Obox4, encodes factor highly expressed...
Although ovarian theca cells play an indispensable role in folliculogenesis by providing follicular structural integrity and steroid substrates for estrogen production, little information is available about their recruitment, growth, differentiation because immature forms have not been identified. We isolated putative thecal stem with the ability to self-renew differentiate vivo vitro. They are similar fibroblasts morphology proliferate vitro as round colonies a homogenous cell population....
Spermatogonial stem cells (SSCs) undergo self-renewal division, which can be recapitulated in vitro. Attempts to establish serum-free culture conditions for SSCs have met with limited success. Although we previously reported that cultured without serum on laminin-coated plates, the growth rate and SSC concentration were relatively low, made it inefficient culturing large numbers of SSCs. In this study, report a novel medium showed improved maintenance. We used Iscove modified Dulbecco...
Abstract Somatic cell nuclear transfer (SCNT) in mammals is an inefficient process that frequently associated with abnormal phenotypes, especially placentas. Recent studies demonstrated mouse SCNT placentas completely lack histone methylation (H3K27me3)-dependent imprinting, but how it affects placental development remains unclear. Here, we provide evidence the loss of H3K27me3 imprinting responsible for enlargement and low birth rates following SCNT, through upregulation imprinted miRNAs....
Primordial germ cells (PGCs) are embryonic cell precursors. Although the developmental potency of PGCs is restricted to lineage, can acquire pluripotency, as verified by in vitro establishment (EG) and vivo production testicular teratomas. PGC-specific inactivation PTEN, which a lipid phosphatase antagonizing phosphoinositide-3 kinase (PI3K), enhances both EG teratoma formation. Here, we analyzed effect serine/threonine AKT, one major downstream effectors PI3K, on PGCs. We used transgenic...
Animals cloned by somatic cell nuclear transfer (SCNT) provide a unique model for understanding the mechanisms of epigenetic reprograming to state totipotency. Though many phenotypic abnormalities have been demonstrated in animals, underlying are not well understood. In this study, we performed transcriptome-wide allelic expression analyses brain and placental tissues mice. We found that Gab1, Sfmbt2 Slc38a4 showed loss imprinting all mice analyzed, which might be involved placentomegaly...
Male infertility is most commonly caused by spermatogenic defects or insufficiencies, the majority of which are as yet cureless. Recently, we succeeded in cultivating mouse testicular tissues for producing fertile sperm from spermatogonial stem cells. Here, show that one severe types defect mutant can be treated culture method without any genetic manipulations. The Sl/Sl d used a model such male infertility. testis has only primitive spermatogonia germ cells, lacking sign spermatogenesis...
The placenta is critical in mammalian embryonic development because the embryo’s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through it. However, molecular mechanisms underlying this acid are poorly understood. In study, we focused system A transporters Slc38a1 /SNAT1, Slc38a2 /SNAT2, and Slc38a4 /SNAT4, which carry neutral, short-side-chain to determine their involvement placental or development. triple-target CRISPR screen identified /SNAT4 as...
Genomic imprinting regulates parental origin-dependent monoallelic gene expression. It is mediated by either germline differential methylation of DNA (canonical imprinting) or oocyte-derived H3K27me3 (noncanonical in mice. Depletion Eed, an essential component Polycomb repressive complex 2, results genome-wide loss oocytes, which causes noncanonical (LOI) embryos. Although Eed maternal KO (matKO) embryos show partial lethality after implantation, it unknown whether LOI itself contributes to...