Genetic Evidence that Dorsal Spinal Oligodendrocyte Progenitor Cells are Capable of Myelinating Ventral Axons Effectively in Mice

In the developing spinal cord,the majority of oligodendrocyte progenitor cells(OPCs)are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog(Shh)signaling pathway,whereas a small subset of OPCs are generated from the dorsal neuroepithelial cells independent of the Shh pathway.Although dors allyderived OPCs(dOPCs)have been shown to participate in local axonal myelination in the dorsolateral regions during development,it is not known whether they are capable of migrating into the ventral region and myelinating ventral axons.In this study,we confirmed and extended the previous study on the developmental potential of dOPCs in the absence of ventrally-derived OPCs(vOPCs).In NestinSmo conditional knockout(cKO)mice,when ventral oligodendrogenesis was blocked,dOPCs were found to undergo rapid amplification,spread to ventral spinal tissue,and eventually differentiated into myelinating OLs in the ventral white matter with a temporal delay,providing genetic evidence that dOPCs are capable of myelinating ventral axons in the mouse spinal cord.

Aberrant nuclear lamina contributes to the malignancy of human gliomas

Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.