title: Lengthening the G(1) phase of neural progenitor cells is concurrent with an increase of symmetric neuron generating division after stroke.
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 (T(C)) 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 T(C) resulted from a decrease of the G(1) phase because the G(2), M, and S phases were unchanged. In addition, during this period, reduction of the G(1) phase was concomitant with an increase in the P fraction, whereas an augmentation of the Q fraction was associated with lengthening of the G(1) 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 G(1) leads to daughter cells exiting the cell cycle and differentiating into neurons.
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Zhang
authors.forename: Zheng G
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Yvonne
authors.initials: Y
authors.lastname: LeTourneau
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D016193:G1 Phase / Q000502:physiology*; D007700:Kinetics; D009474:Neurons / Q000166:cytology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D020521:Stroke / Q000473:pathology*