Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos.
Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos.
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DOI：
10.1016/j.cell.2016.03.023
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发表时间：
2016-05-05
期刊：
影响因子：
64.5
通讯作者：
Lanner F
中科院分区：
文献类型：
--
作者：
Petropoulos S;Edsgärd D;Reinius B;Deng Q;Panula SP;Codeluppi S;Plaza Reyes A;Linnarsson S;Sandberg R;Lanner F
小鼠研究有助于形成我们目前对早期细胞谱系决定的理解;然而，对早期人类发育的类似见解非常有限。在这里，我们提出了一个全面的人类胚胎发育的转录图谱，包括来自88个人类植入前胚胎的1，529个单个细胞的测序转录组。这些数据表明，细胞经历谱系特异性基因共表达的中间状态，随后同时建立滋养外胚层、上胚层和原始内胚层谱系，这与胚泡形成一致。所有三个谱系的雌性细胞在植入前实现X染色体RNA水平的剂量补偿。然而，与小鼠相反，XIST在整个表达抑制的过程中从两个等位基因转录，并且X染色体基因在剂量补偿进行时保持双等位基因表达。我们设想广泛的用途，这一转录图谱在未来的研究人类发展以及干细胞研究。来自88个人类植入前胚胎的1，529个个体细胞的转录组人类胚泡中滋养外胚层、原始内胚层和多能性外胚层X染色体剂量补偿的谱系分离人类植入前发育的综合转录图谱揭示了人类滋养外胚层、外胚层和原始内胚层谱系的同时建立以及X染色体剂量补偿的独特特征。
Mouse studies have been instrumental in forming our current understanding of early cell-lineage decisions; however, similar insights into the early human development are severely limited. Here, we present a comprehensive transcriptional map of human embryo development, including the sequenced transcriptomes of 1,529 individual cells from 88 human preimplantation embryos. These data show that cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation. Female cells of all three lineages achieve dosage compensation of X chromosome RNA levels prior to implantation. However, in contrast to the mouse, XIST is transcribed from both alleles throughout the progression of this expression dampening, and X chromosome genes maintain biallelic expression while dosage compensation proceeds. We envision broad utility of this transcriptional atlas in future studies on human development as well as in stem cell research. Transcriptomes of 1,529 individual cells from 88 human preimplantation embryos Lineage segregation of trophectoderm, primitive endoderm, and pluripotent epiblast X chromosome dosage compensation in the human blastocyst A comprehensive transcriptional map of human preimplantation development reveals a concurrent establishment of trophectoderm, epiblast, and primitive endoderm lineages and unique features of X chromosome dosage compensation in human.