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Carnegie Stage 3 - First Trimester
Cleavage - 1st Cell Division

SIZE: 0.1 - 0.2 mm

TIME PERIOD: 1.5 - 3 days post-ovulation

The zygote now begins to cleave, with each division occurring into two cells called blastomeres. The zygote's first cell division begins a series of divisions, with each division occurring approximately every twenty hours. Each blastomere within the zona pellucida becomes smaller and smaller with each subsequent division.

When cell division generates about sixteen cells, the zygote becomes a morula (mulberry shaped). It leaves the fallopian tube and enters the uterine cavity three to four days after fertilization.

Recent research in August 2014, has discovered that a handful of genes are clearly signaling to each other at the two-cell and four-cell stage, which happens within days after an egg has been fertilized by sperm and before the embryo has implanted into the uterus. Among the identified genes are several genes belonging to the WNT signaling pathway, well-known for their role in cell-cell communications.

This research, which used single-cell RNA sequencing to look at every gene in the mouse genome, was published in 2014 in the journal Genome Research. In addition, this group published a paper on analysis of "time-course" single-cell data which is taken at precise stages of embryonic development in the journal of Proceedings of the National Academy of Sciences.

Clustering, in essence, was a tool for describing spatial characteristics in the objects of concern. However, from social to biological studies, researchers’ interests in temporal characteristics often rival their interests in spatial features. Previous efforts to incorporate time information into clustering primarily relied on coding the time information into similarity metrics, thus reducing the problem into the classical paradigm of spatial clustering. The limitation is that the clustering outcomes are often time invariant. Here, we initiate a class of statistical methods that simultaneously infer spatial and temporal groupings. Such methods explicitly model the time dependencies of clustering indices over time. Our method inferred three genes to be associated with the earliest cell fate decision, which was corroborated by experimental validations.

Both spatial characteristics and temporal features are often the subjects of concern in physical, social, and biological studies. This work tackles the clustering problems for time course data in which the cluster number and clustering structure change with respect to time, dubbed time-variant clustering. We developed a hierarchical model that simultaneously clusters the objects at every time point and describes the relationships of the clusters between time points. The hidden layer of this model is a generalized form of branching processes. A reversible-jump Markov Chain Monte Carlo method was implemented for model inference, and a feature selection procedure was developed. We applied this method to explore an open question in preimplantation embryonic development. Our analyses using single-cell gene expression data suggested that the earliest cell fate decision could start at the 4-cell stage in mice, earlier than the commonly thought 8- to 16-cell stage. These results together with independent experimental data from single-cell RNA-seq provided support against a prevailing hypothesis in mammalian development.

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