Lengthening the G1 Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

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Abstract
The proportion of neural progenitors that remain in ( P fraction) and exit from ( Q fraction) the cell cycle determines the degree of neurogenesis. Using S-phase labeling with 5-bromo-2′-deoxyuridine and a double nucleoside analog-labeling scheme, we measured the cell-cycle kinetics of neural progenitors and estimated the proportion of P and Q fractions in the subventricular zone (SVZ) of adult rats subjected to stroke. Stroke increased SVZ cell proliferation, starting 2 days, reaching a maximum 4 and 7 days after stroke. The cell-cycle length ( TC) of SVZ cells changed dynamically over a period of 2 to 14 days after stroke, with the shortest length of 11 h at 2 days after stroke. The reduction of the TC resulted from a decrease of the G1 phase because the G2, M, and S phases were unchanged. In addition, during this period, reduction of the G1 phase was concomitant with an increase in the P fraction, whereas an augmentation of the Q fraction was associated with lengthening of the G1 phase. Furthermore, approximately 90% of cells that exited the cell cycle were neurons and the population of a pair of dividing daughter cells with a neuronal marker increased from 9% at 2 days to 26% at 14 days after stroke. These data suggest that stroke triggers early expansion of the progenitor pool via shortening the cell-cycle length and retaining daughter cells within the cell cycle, and the lengthening of G1 leads to daughter cells exiting the cell cycle and differentiating into neurons.

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