Molecular Study on Differentiation-Associated Genes Involved in Both Malignant Progression of Glioma and Differentiation of Human Fetal Neural Stem Cells

Correlations of NSCs differentiation and malignant progression of ganglioglioma.

Upper half part: Above: pathological examination of glioma specimens In different malignancy grades during tumor progression (A-C) and expression of 3 genes in these corresponding specimens. A primary tumor (H&E staining, 400 * ): neoplastic neurons, neoplastic astrocytes and binucleate neurons (T) can be seen. Pathological diagnosis was ganglioglioma (WHO grade II). B 1st recurrent tumor(H&E staining, 400 * ): Neoplastic neurons disappeared, while neoplastic glial cells Increased with high density. Nuclear heteromorphism can be seen and chromatin obviously increased. Pathological diagnosis was anaplastic astrocytoma (WHO grade III). C 2nd recurrent tumor (H&E staining, 400x ): Microscopic field was crowded with neoplastic astrocytes, forming into vascular retia of chicken wire permutation, and pseudopalisade formation and multlnucleated giant cells (t) were found. Pathological diagnosis was glioblastoma multiform (WHO grade IV). Below: gene expression ratio values of GLT1, CDC2 and MAPKK4 in gene expression profiling corresponding to the tumor specimens above. Gene expression values rose with malignant progression of glioma.

Lower half part: Above: undifferentiated neural stem cell sphere (NSC), neural stem cells initiating differentiation (* 200), the majority were Nestin’ cells, while the minority were GFAP* cells(D); neuroglial progenitor cells (* 200), GFAP’ cells were predominant, with few NSE* cells and Nestin’ cells (E); terminal differentiated mature astrocytes (GFAP immunofluorescence staining, * 1000) NSE* cells and Nestin’cells could not be found. Below: Expression of three genes, GLT1, CDC2 and MAPKK4 In cells with different differentiation stages, corresponding to the four cell populations mentioned above. Expression levels of these three genes was very low In undifferentiated NSCs sphere (NSC), but Increased In NSCs Initiating differentiation(D), then decreased gradually in neuroglial progenitor cells (E) and astrocytes (F).