Recruited Cells Can Become Transformed and Overtake PDGF-Induced Murine Gliomas In Vivo during Tumor Progression

Gliomas are thought to form by clonal expansion from a single cell-of-origin, and progression-associated mutations to occur in its progeny cells. Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration.We performed lineage tracing in a retrovirally mediated, molecularly and histologically accurate mouse model of hPDGFb-driven gliomagenesis. We were able to distinguish cells in the tumor that were derived from the cell-of-origin from those that were not. Phenotypic, tumorigenic and expression analyses were performed on both populations of these cells. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population not derived from the cell-of-origin within glioma microenvironment to dominate regions of the tumor, with essentially no contribution from the progeny of glioma cell-of-origin. Moreover, the recruited cells can give rise to gliomas upon transplantation and passaging, acquire polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, aid progeny cells in glioma initiation upon transplantation, and become independent of PDGFR signaling.These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become bona fide tumor, and deviate from the generally established view of gliomagenesis

Formal statement of the special principle of relativity

While there is a longstanding discussion about the interpretation of the extended, general principle of relativity, there seems to be a consensus that the special principle of relativity is absolutely clear and unproblematic. However, a closer look at the literature on relativistic physics reveals a more confusing picture. There is a huge variety of, sometimes mataphoric, formulations of the relativity principle, and there are different, sometimes controversial, views on its actual content. The aim of this paper is to develop a precise language in order to provide a precise formulation of the principle. In view of the fact that the special relativity principle is considered as a universal meta-law, which must be valid for all physical laws in all situations, we try to keep the formalism as general as possible. The benefit of the formal reconstruction is that it makes explicit all the necessary conceptual components of the principle; it brings out many subtle details and the related conceptual problems