Molecular characterization of cell identity and the annotation of the GRNs using next-generation sequencing technologies have opened up new avenues to dissect the developmental events and reconstruct the cell lineage in unprecedented detail. Though limited by the inherent incompleteness of low-throughput methods, these factors have been cornerstones for high-throughput and systematic studies to build reliable networks and to verify computational modeling and simulation. A compendium of TFs and molecular determinants that are involved in pluripotency maintenance and cell fate determination has been extensively described (summarized inĨ). The particular architecture and dynamics of cell type-specific GRNs that contribute profoundly to tissue organization during development have been conventionally studied by a gene-by-gene approach (for example, genetic manipulation and lineage tracing). Systematic approaches to study transcription regulation for the development process Moreover, there exist intricate causal relationships between the cell type-specific GRNs and the phenotypic outputs during embryo development and stem cell differentiation, making the understanding of gene regulation a demanding task. It is now known that during this complex process, stem cell hierarchical systems are established with step-wise restricted differentiating capacities following the orchestration of transcriptional regulation, through which the encoding and coordinating morphogenetic outcomes are attainedĦ. The remarkable similarity in the stem cell behavior of animal species during periods of early embryonic development points to the existence of an inherent conserved molecular principle underpinning the cell fate determinationĥ. Afterwards, the embryo goes through a continuum of pluripotent states such as the continuous transition from naïve, formative to primed pluripotencyĢ and forms the primary germ layers that eventually set the body plan The ICM gives rise to the epiblast and the primitive endoderm at the second lineage segregation. ICM cells are a pluripotent cell population from which all cell types in the embryo proper, as well as tissues of the extraembryonic fetal membranes, will be generated, while the trophectoderm will contribute to tissues of the fetal components of placenta. The first lineage segregation occurs shortly after fertilization, during which the totipotent blastomeres give rise to the inner cell mass (ICM) and the trophectoderm. In mouse embryo development, for example, the zygote cell undergoes sequential cell divisions and two major cell fate segregations before proceeding to germ layer determination. In this article, we briefly review the regulation of early development and focus on recent advances of enabling technologies and methodologies-for example, single-cell RNA sequencing (scRNA-seq) and spatial transcriptome-in characterizing the GRNs of early embryo development.Ĭell fate determination and lineage specification of early embryo developmentĮarly embryo development in vertebrate animals is conserved in molecular regulationsġ. Moreover, building detailed predictive computational models of GRNs based on the high-dimensional data is challenging. However, despite accumulated studies in molecular, cellular, and animal levels that have profoundly revealed the key players during early development, the dynamic interaction of GRNs-with their large number of components and even larger number of potential interactions between those components-demands a systematic and high-dimensional approach. The activity of the transcription factors (TFs), microRNAs, and related gene regulatory networks (GRNs)-as significant intrinsic regulators-is essential for the maintenance of pluripotent states and orchestrated specification of progenitor fates. In vivo stem cell lineage (that is, the normal developmental processes), which generates the authentic and functional cell types with high efficiency.Įmbryonic early development is tightly controlled by intrinsic and extrinsic factors. However, one of the major obstacles for stem cell therapy is the low purity with low efficiency in obtaining functional cells because of the lack of a complete understanding of In recent years, stem cells and stem cell-based translational applications have been recognized as a promising strategy in the future of medicine to tackle incurable situations by conventional treatment (for example, neural degenerative diseases and organ failure).
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