Purified astrocytes promote the in vitro division of a bipotential glial progenitor cell.

Abstract

Optic nerves of neonatal rats contain a bipotential glial progenitor cell which can be induced by tissue culture conditions to differentiate into either an oligodendrocyte (the myelinforming cell of the CNS) or a type 2 astrocyte (an astrocyte population found only in the myelinated tracts of the CNS).In our previous studies most oligodendrocyte-type 2 astrocyte (0-2A) progenitor cells differentiated within 3 days in vitro with relatively little division of the progenitors or their differentiated progeny. We have now found that the O-2A progenitors are stimulated to divide in culture by purified populations of type 1 astrocytes, another glial cell-type found in the rat optic nerve. This cell-cell interaction appears to be mediated by a soluble factor(s) and results in the production of large numbers of both progenitor cells and oligodendrocytes. As type 1 astrocytes are the major glial cell-type in the optic nerve when oligodendrocytes first begin to be produced in large numbers in vivo, our results suggest that this astrocyte subpopulation may play an important role in expanding the oligodendrocyte population during normal development.

Molecular cloning of rat mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase and detection of the corresponding mRNA and of those encoding the remaining enzymes comprising the ketogenic 3-hydroxy-3-methylglutaryl-CoA cycle in central nervous system of suckling rat

“…The methods of Noble and Murray [23] and Peuchen et al [24] were followed for the isolation of neonatal and adult astrocytes from cortices of 1-2-day-old or 6-8-week-old rats. In both instances cells were harvested after 12-14 days in itro.…”

TPO1, a Member of a Novel Protein Family, Is Developmentally Regulated in Cultured Oligodendrocytes

“…The resulting populations consisted routinely of~-~96%A2B5~/<4%04 (early progenitors), >85% O4~/<l%01 (late progenitors = prooligodendrocytes), >80% 01 + / <1% MBP -(immature OLs), and >90% 01~I>45%MBP~(maturing OLs). Cultures of cortical, glial fibrillary acidic protein + (GFAP~) astrocytes were obtained as previously described (Noble and Murray, 1984;Gard and Pfeiffer, 1990) and were essentially devoid of OLs.…”

Type-2 astrocyte development in rat brain cultures is initiated by a CNTF like protein produced by type-1 astrocytes

“…In vitro studies suggest that the timing and direction of 0-2A progenitor cell development are greatly influenced by environmental factors, In cultures of perinatal rat optic nerve cells, for example, which contain all three types of macroglial cells and their precursors but no neurons, the timing of 0-2A progenitor cell differentiation into oligodendrocytes has been shown to be regulated by a growth factor secreted by type-1 astrocytes (Noble and Murray, 1984;Raff et aI., 1985), The growth factor, recently identified as platelet derived growth factor (PDGF) (Richardson et aI., 1988), stimulates the proliferation of 0-2A progenitor cells and prevents their premature differentiation into oligodendrocytes. Even in the continuous presence of PDGF, however, progenitor cells eventually stop dividing and differentiate into oligodendrocytes, a sequence precisely timed by a mechanism that appears to be intrinsic to the progenitor cell (Raff et aI., 1988), Oligodendrocyte differentiation occurs in optic nerve cultures grown in defined, serum-free medium (Raff et aI., 1983bl.…”