Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord

By P. Horner, A. E. Power, Gerd Kempermann, H. Kuhn, T. Palmer, Jürgen Winkler, L. Thal, Fred H. Gage. Journal of Neuroscience, 2000

799 citations recorded by the source corpus.

The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5–7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells dividein situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes.

Subfields: Cancer Research, Developmental Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/dc8615dbf82a25c4adda7ea5becb9cb901b558bb

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Citations in the corpus

The Biology of Regeneration Failure and Success After Spinal Cord Injury. (2018, background): “They are characterized by their branched processes and ability to normally self-renew in adulthood (172).”
NG2 cells generate both oligodendrocytes and gray matter astrocytes (2007, background): “In these areas, which include the juvenile and adult spinal cord, BrdU-incorporated cells were seen to turn into mature oligodendrocytes over time in normal and demyelinated tissues (Bu et al., 2004; Horner et al., 2000; Watanabe et al., 2002; McTigue et al., 2001).”
Why does remyelination fail in multiple sclerosis? (2002, background): “First, proliferating cells that are likely to be OPC”
Vascular niche for adult hippocampal neurogenesis (2000, background): “Although the 2-hour pulse of BrdU labeled mainly single cells, animals that were allowed to survive 24 hours after a single injection showed that the single labeled cells transitioned into BrdU-labeled daughter cell pairs (not shown, Horner et al., 2000).”
Astrocytes: biology and pathology (2009, background): “astrocytes and it appears that the majority of astrocytes are post-mitotic and long-lived [33, 45, 97, 167].”
Astroglia induce neurogenesis from adult neural stem cells (2002, background): “Outside these two regions, proliferating cells give rise to new glia but not to neurons in the intact adult CN”
Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells (2006, background): “In vivo, no adult neurogenesis can be found in the rodent spinal cord (Horner et al. 2000).”
Origin of new glial cells in intact and injured adult spinal cord. (2010, background): “The remaining BrdU-labeled cells are mainly microglia and blood vessel-associated cells (Horner et al., 2000).”
Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation (2006, background): “The adult CNS contains a precursor cell population that responds to demyelination by undergoing rapid proliferation, migration, and differentiation into new oligodendrocytes (Horner et al., 2000; Franklin, 2002).”
Spinal Cord Injury Reveals Multilineage Differentiation of Ependymal Cells (2008, background): “Studies using indirect techniques have suggested that the neural stem cell potential in the adult rodent spinal cord resides in the white matter parenchyma [6,7] or close to the central canal, either in the ependymal layer [8] or subependymally [9].”
Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity (2009, background): “Second, pulse-chase labelling of proliferating cells using 5-bromo-2′-deoxyuridine (BrdU) revealed that the number of BrdU+NG2+ cells decreases and that of BrdU+ oligodendrocytes increases over time after BrdU injectio”
NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. (2010, background): “, 1993), BrdU (Horner et al., 2000), and retrovirus (Levison et al.”
Adult Spinal Cord Stem Cells Generate Neurons after Transplantation in the Adult Dentate Gyrus (2000, background): “We have demonstrated recently that the adult rat spinal cord contains large numbers of dividing cells in vivo that give rise to glia but not neurons (Horner et al., 2000).”
Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain (2008, background): “Glial progenitors that actively proliferate in the adult cortex even before injury, such as NG2 or PDGFR cells (3, 4, 8, 33), are not capable of forming multipotent neurospheres.”
Doublecortin expression levels in adult brain reflect neurogenesis (2005, background): “agreement with the fact that in the intact spinal cord, as in the lesioned, no spontaneous neurogenesis has been reported to date (Horner et al., 2000).”