Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

SUMMARYRadial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted “intermediate” precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

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Skin-Derived Precursor Cells as an In Vitro Modelling Tool for the Study of Type 1 Neurofibromatosis

Stem Cells International ◽

10.1155/2012/646725 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Araika Gutiérrez-Rivera ◽

Haizea Iribar ◽

Anna Tuneu ◽

Ander Izeta

Keyword(s):

In Vitro Study ◽

Neurofibromatosis Type ◽

Precursor Cells ◽

Cell Of Origin ◽

Wild Type ◽

Multipotent Progenitor Cells ◽

Clonal Origin ◽

Lines Of Evidence

The most characteristic feature of neurofibromatosis type 1 (NF1) is the development of neurofibromas. It has been suggested that these tumors are caused by somatic inactivation of the wild-typeNF1allele, but the cell that originally suffers this mutation remains controversial. Several lines of evidence support the clonal origin of these tumors, and it has been recently suggested that skin-derived precursor cells (SKPs) could be the cell of origin of dermal neurofibromas. Nullizygous (NF1−/−) SKPs do give rise to neurofibromas when transplanted to heterozygous mice. Moreover, a nullizygous population of cells that is S100βnegative is present in human neurofibromas, andNF1+/−multipotent progenitor cells are seemingly recruited to the tumor. This evidence supports the neurofibroma stem cell hypothesis and a putative involvement of SKPs in the aetiopathogenesis of the disease, suggesting that SKPs could become a valuable tool for the in vitro study of NF1.

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Oligodendrocyte precursor cells prune axons in the mouse neocortex

10.1101/2021.05.29.446047 ◽

2021 ◽

Author(s):

JoAnn Buchanan ◽

Leila Elabaddy ◽

Forrest Collman ◽

Nikolas L. Jorstad ◽

Trygve E. Bakken ◽

...

Keyword(s):

Large Scale ◽

Cell Types ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Structural Refinement ◽

Terminal Axon ◽

Glial Progenitors ◽

Single Nucleus ◽

Oligodendrocyte Precursor ◽

Mouse Visual Cortex

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This transformation is facilitated by the engulfment and degradation of excess axonal branches and inappropriate synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia has made it difficult to determine the contribution of these and other glial cell types to this process. Here, we used large scale, serial electron microscopy (ssEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded terminal axon branches and included numerous phagolysosomes (PLs) containing fragments of axons and presynaptic terminals. Single- nucleus RNA sequencing indicated that cortical OPCs express key phagocytic genes, as well as neuronal transcripts, consistent with active axonal engulfment. PLs were ten times more abundant in OPCs than in microglia in P36 mice, and declined with age and lineage progression, suggesting that OPCs contribute very substantially to refinement of neuronal circuits during later phases of cortical development.

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CNS glial progenitors and schwann cells in neurofibromatosis Type 1

Journal of Neurochemistry ◽

10.1046/j.1471-4159.81.s1.48_2.x ◽

2008 ◽

Vol 81 ◽

pp. 2-2

Author(s):

N. Ratner ◽

S. J. Miller ◽

B. Ling ◽

Y. N. Huang ◽

M. R. Bennett ◽

...

Keyword(s):

Schwann Cells ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Glial Progenitors

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Multicentric pleomorphic xanthoastrocytoma in a patient with neurofibromatosis Type 1

Journal of Neurosurgery ◽

10.3171/jns.2005.102.2.0376 ◽

2005 ◽

Vol 102 (2) ◽

pp. 376-381 ◽

Cited By ~ 31

Author(s):

Stephan Saikali ◽

Anne Le Strat ◽

Anne Heckly ◽

Nathalie Stock ◽

Jean-Marie Scarabin ◽

...

Keyword(s):

Malignant Transformation ◽

Neurofibromatosis Type 1 ◽

Unusual Case ◽

Neurofibromatosis Type ◽

Pleomorphic Xanthoastrocytoma ◽

Precursor Cells ◽

Cerebellar Tumor ◽

Content Type ◽

Fine Print

✓ The authors report an unusual case of multicentric pleomorphic xanthoastrocytoma (PXA) in a 36-year-old woman with neurofibromatosis Type 1 (NF1). Both lesions were diagnosed as PXA but demonstrated different neuroimaging features and very different outcomes. Although the occipital lesion was cured surgically, the cerebellar tumor recurred three times and underwent malignant transformation into an anaplastic oligodendroglioma. The authors discuss the causes of PXA and suggest that it could originate from common bipotential precursor cells with two phenotypes.

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