Reconstructing Somatic Chromosomes

重建体细胞染色体

• 批准号: 10772559
• 负责人: SHOUKHRAT M MITALIPOV
• 金额: $ 65.99万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-26 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10772559
• 关键词: Base Sequence; Biological; Cell Cycle; Cell Nucleus; Cell division; Cells; Characteristics; Chromatids; Chromatin; Chromosome Pairing; Chromosomes; Cytoplasm; DNA Double Strand Break; DNA biosynthesis; Development; Diploid Cells; Diploidy; Disease; Elderly; Embryo; Embryo Research; Embryo Transfer; Epigenetic Process; Event; Fertilization; Frequencies; Future; G1 Arrest; Gametogenesis; Generations; Genetic; Genetic Recombination; Genetic Transcription; Genome; Germ Cells; Goals; Haploidy; Homologous Gene; Human; Hybrid Cells; In Vitro; Inbred Strains Mice; Infertility; Interphase; Mammals; Meiosis; Metaphase; Mus; Oocytes; Pathway interactions; Patients; Ploidies; Pre-implantation Embryo Development; Primates; Process; Production; Research; Role; Skin; Somatic Cell; Therapeutic; Totipotency; Totipotent; Transplantation; Triploidy; daughter cell; directed differentiation; egg; embryonic stem cell; imprint; induced pluripotent stem cell; infertility treatment; insight; mouse model; novel; offspring; premature; programs; reproductive; segregation; somatic cell nuclear transfer; sperm cell; success; therapy development; zygote

Project Summary: Somatic cell nuclear transfer (SCNT) replaces haploid meiotic chromosomes in metaphase (MII)-arrested oocytes with diploid interphase chromatin from somatic cells. Such SCNT oocytes are diploid and are not suitable for fertilization due to triploidy. However, our preliminary studies indicate that SCNT oocytes are capable of forming premature meiotic spindles consisting of paired single-chromatid chromosomes and subsequent activation or fertilization can induce segregation of somatic chromosomes into a pseudo polar body. Our research will determine if somatic homolog pairing and recombination in mouse SCNT oocytes can be induced by DNA double strand breaks and develop future therapeutic approaches for infertility treatments.

项目概要： 体细胞核移植（SCNT）取代中期（MII）的单倍体减数分裂染色体-停滞 来自体细胞的具有二倍体间期染色质的卵母细胞。这种SCNT卵母细胞是二倍体， 由于三倍体而受精。然而，我们的初步研究表明，SCNT卵母细胞能够 形成由成对的单染色单体染色体组成的过早减数分裂纺锤体， 激活或受精可诱导体细胞染色体分离成假极体。我们的研究 将确定小鼠SCNT卵母细胞中的体细胞同源物配对和重组是否可以由DNA诱导 双链断裂，并开发未来的治疗不孕症的治疗方法。