The current study established that a transgenic mouse model, Nes-CreERT2 Tdtomato, is of use to trace the fate of nestin-expressing cells in glioma progression and postnatal brain development. Through a series of cell type identification tests, using immunofluorescence labelling and confocal microscopy, it was shown that these nestin-positive cells generate new pericytes, but initially do not have a pericyte identity, this is corroborated by the following findings:
(1) In the Nes-CreERT2 Tdtomato mouse model, the number of traced cells (RFP positive cells) increased during the intracranial tumor growth. At an early time point (7 days) few of the RFP positive cells co-localized with pericyte markers while at a later time point (21 days) most of the RFP positive cells co-localized with pericyte markers, which indicated that the new pericytes in glioma derived from the pericyte progenitor cells (defined as RFP positive and pericyte marker negative cells) in the Nes-CreERT2 Tdtomato mouse model;
(2) In the JnesCreERT2 Tdtomato mouse model, the traced cells were found to express astrocyte-markers like GFAP but not pericyte markers, which indicated that the traced cells in the JnesCreERT2 Tdtomato mouse model were originally neural stem cells rather than pericyte progenitor cells. Hence, only the Nes-CreERT2 Tdtomato mouse model is useful to study pericyte development in the brain.
(3) The cells traced with the NesCreERT2-tdTomato mouse model over a postnatal period develop into pericytes in the brain, which indicates that the NesCreERT2-tdTomato strain is a useful model to trace the pericyte lineage both in pathological neoangiogenesis during glioma growth and in physiological postnatal angiogenesis.
(4) In this study RFP-expressing pericyte marker positive cells were detected in the postnatal mouse retina, indicating that RFP-traced pericytes play an important role in both pathological angiogenesis and physiological vascular development of retina
