小柯机器人

英国弗朗西斯·克里克研究所James M. A. Turner课题组取得一项新突破。他们揭示了的有袋动物胚胎发育和X染色体失活单细胞转录组图谱。相关论文于2020年8月19日在线发表于国际学术期刊《自然》杂志上。

研究人员利用单细胞RNA测序对有袋动物灰短尾负鼠（Monodelphis domestica）的胚胎发育和X染色体失活进行了分析。研究人员揭示了表皮细胞、原始内胚层和滋养外胚层的发育轨迹和转录特征，并鉴定了真兽亚纲动物-有袋动物分离之前深度保守的谱系特异标记。RSX包被和X染色体失活在发育早期快速产生。该研究结果支持以下假说：在具有早期X染色体失活的生物中，印迹X染色体失活可阻止双等位基因X沉默。研究人员确定由活跃X染色体表达的RSX反义转录物XSR可能是印迹X染色体失活的调节因子。该研究数据集在进化上提供了对哺乳动物胚胎发育和X剂量补偿的新见解。

研究人员表示，胚胎单细胞RNA测序可以在前所未有的分辨率水平揭示发育过程中的转录情况。迄今为止，关于哺乳动物胚胎单细胞RNA测序的研究主要集中在真哺乳亚纲动物。对哺乳动物之外群体的分析有可能发现高度保守的谱系特征和多能性因素，并且可以扩展人们对X剂量补偿的理解。大约在1.6亿年前，后哺乳下纲（有袋类）哺乳动物与真兽亚纲哺乳动物分离。它们具有独特的发育特征，包括晚期着床和印迹X染色体失活，这与XIST样非编码RNA RSX3的表达有关。

附：英文原文

Title: A single-cell transcriptome atlas of marsupial embryogenesis and X inactivation

Author: Shantha K. Mahadevaiah, Mahesh N. Sangrithi, Takayuki Hirota, James M. A. Turner

Issue&Volume: 2020-08-19

Abstract: Single-cell RNA sequencing of embryos can resolve the transcriptional landscape of development at unprecedented resolution. To date, single-cell RNA-sequencing studies of mammalian embryos have focused exclusively on eutherian species. Analysis of mammalian outgroups has the potential to identify deeply conserved lineage specification and pluripotency factors, and can extend our understanding of X dosage compensation. Metatherian (marsupial) mammals diverged from eutherians around 160 million years ago. They exhibit distinctive developmental features, including late implantation1 and imprinted X chromosome inactivation2, which is associated with expression of the XIST-like noncoding RNA RSX3. Here we perform a single-cell RNA-sequencing analysis of embryogenesis and X chromosome inactivation in a marsupial, the grey short-tailed opossum (Monodelphis domestica). We resolve the developmental trajectory and transcriptional signatures of the epiblast, primitive endoderm and trophectoderm, and identify deeply conserved lineage-specific markers that pre-date the eutherian–marsupial divergence. RSX coating and inactivation of the X chromosome occurs early and rapidly. This observation supports the hypothesis that—in organisms with early X chromosome inactivation—imprinted X chromosome inactivation prevents biallelic X silencing. We identify XSR, an RSX antisense transcript expressed from the active X chromosome, as a candidate for the regulator of imprinted X chromosome inactivation. Our datasets provide insights into the evolution of mammalian embryogenesis and X dosage compensation. Single-cell RNA-sequencing analysis of embryogenesis and X chromosome inactivation in the opossum (Monodelphis domestica) resolves the developmental trajectory of a marsupial, and sheds light on the evolution of embryogenesis in mammals.

DOI: 10.1038/s41586-020-2629-6

Source: https://www.nature.com/articles/s41586-020-2629-6

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