Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing

By Zhigang Xue, K. Huang, Chaochao Cai, Ling-bo Cai, Chun-yan Jiang, Yun Feng, Zhenshan Liu, Qiao Zeng, Liming Cheng, Y. Sun and 3 more. Nature, 2013

930 citations recorded by the source corpus.

Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/09f7b140f4355fb4e6525ca173b02e1661aca263

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Citations in the corpus

The technology and biology of single-cell RNA sequencing. (2015, methodology): “Micromanipulation techniques can be used to capture single cells from samples with few cells, such as the early embryo (Grindberg et al., 2013; Tang et al., 2009; Xue et al., 2013; Yan et al., 2013).”
Design and computational analysis of single-cell RNA-sequencing experiments (2016, methodology): “Specifically, many scRNA-seq studies use median normalization [47 – 51] or a similar method [52, 53].”
Single-cell RNA-seq: advances and future challenges (2014, positive): “Single-cell RNA-seq studies have enabled a global analysis of early mammalian development (93,134,139–141), helping to substitute hypothesis-with discovery-driven science.”
Modelling dropouts for feature selection in scRNASeq experiments (2016, background): “Xue Mouse embryos Development stage Poly-A selected RPKMs 17 30% [16] GSE44183”
Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells (2015, methodology): “Single-cell RNA-seq is now commonly used to study cell differentiation 15,24 .”
Gene co-expression analysis for functional classification and gene–disease predictions (2017, methodology): “early development, but diverge at a later stage [12].”
Single-cell transcriptome sequencing: recent advances and remaining challenges (2016, background): “Most commonly, genes are grouped into co-regulated “modules” on the basis of expression profile similarity 16,52,75,86,87,103 (Figure 1D).”
KRAB zinc finger proteins (2017, background): “…the tightly orchestrated transcription of TEcontaining loci during this period (Corsinotti et al., 2013; Theunissen et al., 2016; Macfarlan et al., 2012; Fort et al., 2014; Gifford et al., 2013; Goke et al., 2015; Grow et al., 2015; Kunarso et al., 2010; Xue et al., 2013; Yan et al., 2013).”
Defining cell types and states with single-cell genomics (2015, background): “For example, several groups have studied developing embryos (Hashimshony et al. 2012; Grindberg et al. 2013; Xue et al. 2013) with single-cell transcriptomics by projecting them onto the first two principal components.”