Postnatal NG2 proteoglycan–expressing progenitor cells are intrinsically multipotent and generate functional neurons

TLDR

Neurogenesis persists in the adult mammalian CNS, yet the identity of the postnatal progenitor cells that generate new neurons remains elusive. In transgenic mice, NG2+ progenitor cells expressing 2′,3′‑cN‑PDE are multipotent in vitro, generating neurons, astrocytes, and oligodendrocytes, and in vivo they proliferate in the hippocampus to produce functional GABAergic neurons. NG2+ progenitors display rapid, intrinsically multipotent differentiation, producing functional GABAergic neurons in the hippocampus and likely contribute to adult hippocampal neurogenesis.

Abstract

Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan–positive progenitor cells that express the 2′,3′-cyclic nucleotide 3′-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.