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人类胚胎基因组激活始于一细胞阶段
作者:小柯机器人 发布时间:2021/12/26 12:57:06

英国巴斯大学Anthony C.F. Perry等研究人员合作发现,人类胚胎基因组激活始于一细胞阶段。2021年12月21日,《细胞—干细胞》杂志在线发表了这项成果。

据研究人员介绍,在人类胚胎中,转录的启动(胚胎基因组激活[EGA])发生在八细胞阶段,但其确切的时间和概况还不清楚。
 
为了解决这个问题,研究人员对人类中期II卵母细胞和双核(2PN)单细胞胚胎的基因表达进行了深度分析。高分辨率的单细胞RNA测序揭示了以前无法企及的卵细胞到胚胎的基因表达变化。这证实了受精后转录本的耗竭(母源RNA降解),但也发现了数百个剪接转录本的低幅度上调。基因表达分析预测了胚胎过程,包括细胞周期进展和染色体维持,以及转录激活因子,包括癌症相关基因调节因子。转录在异常的单核(1PN)和三核(3PN)单细胞胚胎中被破坏。这些发现表明,人类胚胎的转录在一细胞阶段开始,比以前认为的要早。基因上调的模式有望阐明人类发育开始时的过程,对表观遗传、干细胞衍生的胚胎和癌症有影响。
 
附:英文原文

Title: Human embryonic genome activation initiates at the one-cell stage

Author: Maki Asami, Brian Y.H. Lam, Marcella K. Ma, Kara Rainbow, Stefanie Braun, Matthew D. VerMilyea, Giles S.H. Yeo, Anthony C.F. Perry

Issue&Volume: 2021-12-21

Abstract: In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by the eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in human metaphase II oocytes and bipronuclear (2PN) one-cell embryos. High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo gene expression changes. This confirmed transcript depletion following fertilization (maternal RNA degradation) but also uncovered low-magnitude upregulation of hundreds of spliced transcripts. Gene expression analysis predicted embryonic processes including cell-cycle progression and chromosome maintenance as well as transcriptional activators that included cancer-associated gene regulators. Transcription was disrupted in abnormal monopronuclear (1PN) and tripronuclear (3PN) one-cell embryos. These findings indicate that human embryonic transcription initiates at the one-cell stage, sooner than previously thought. The pattern of gene upregulation promises to illuminate processes involved at the onset of human development, with implications for epigenetic inheritance, stem-cell-derived embryos, and cancer.

DOI: 10.1016/j.stem.2021.11.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00484-7

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx