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P119. Properties of neocortical progenitor cells along developmental stages as revealed by single cell gene expression profiles

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DOI: 10.1016/j.diff.2010.09.125


In mammalian cerebral cortex, neural progenitor cells change their cytogenetic behavior dynamically as development proceeds: while progenitors in early embryonic days mainly generate two progenitor cells in a symmetric manner, those in the middle stage give rise to two different types of daughters in an asymmetric manner (i.e., a stem-like daughter cell and a daughter cell to soon proceed to differentiation). To understand how this stage-dependent cytogenesis is achieved, we sought to identify genes that are expressed by cortical progenitor cells in a temporally regulated manner. We first compared the gene expression profiles of progenitor cells isolated from mouse cortex at E11, E14 and E16 using the single-cell cDNA amplification method followed by microarray analysis. Single-cell gene expression profiles could classify the neocortical progenitor cells into the apical (stem-like) progenitors and the basal (non-stem-like) progenitors at all developmental stages examined. Next, we performed the unsupervised principal component analysis (PCA) of all stages apical progenitor cells, found that the expression pattern of E11 apical progenitors is distinct from that of E14 apical progenitors. This result suggests that apical progenitors may change their property between E11 and E14. Based on these results, we identified a set of genes whose expression increases or decreases during this E11–E14 period. To ask whether these genes are involved in the stage-dependent change of cytogenesis pattern (from symmetric or purely proliferative to asymmetric or more differentiating), we are now doing “heterochronic” in utero erectroporation experiments. For example, a gene that is normally expressed strongly by E14 apical progenitors but not by E11 apical progenitors is artificially expressed in the cortical wall at E10–E11.

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