Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/17992
Title: Regulatory mechanisms defining the blastocyst cell lineages
Authors: GUO GUOJI
Keywords: Blastocyst, Trophectoderm, Epiblast, Primitive endoderm, Single cell analysis, Cdx2
Issue Date: 11-Aug-2009
Source: GUO GUOJI (2009-08-11). Regulatory mechanisms defining the blastocyst cell lineages. ScholarBank@NUS Repository.
Abstract: The first cellular differentiation event in mouse development leads to the formation of the blastocyst consisting of the inner cell mass (ICM) and a functional epithelium (trophectoderm; TE). The ICM shortly thereafter gives rise to the pluripotent epiblast (EPI) and the extra-embryonic primitive endoderm (PE). The molecular mechanisms that regulate the differentiation of totipotent blastomeres to the three distinct cell types remain unclear. Here I applied quantitative single cell technology to profile the expression of 48 genes, in parallel, from individual cells harvested throughout preimplantation development. I found that blastomeres at the 16 cell stage abundantly express numerous transcription factors that subsequently become lineage-restricted. Early differential gene expression patterns suggest a crucial role of position and signalling events during cell fate decisions; this was then validated by specific pathway inhibition in the system. Finally, analysis on Cdx2 (a key TE lineage transcription factor) knockout blastocysts revealed the hierarchy of the genetic network that drives the initial lost of totipotency. I show that Cdx2 activates TE transcriptional program while repressing the totipotent network. The results integrate the external signalling pathways with the core internal transcriptional network through the blastocyst lineages differentiation. My work dramatizes the power of new microgenomic technologies to provide insight into developmental mechanisms.
URI: http://scholarbank.nus.edu.sg/handle/10635/17992
Appears in Collections:Ph.D Theses (Open)

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