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16.03.21 Tracing cell fate in developing mouse cortex suggests lineage origin of brain tumours

last modified Apr 03, 2021 01:35 PM
Tracing the fate of sister cells in the developing mouse cortex, the Simons lab and collaborators in Beijing uncover the cellular dynamics during gliogenesis, defining a stereotypic phase of astrocyte and oligodendrocyte production. These results suggest the cellular and lineage origin of primary brain tumour
16.03.21 Tracing cell fate in developing mouse cortex suggests lineage origin of brain tumours

Video S1 still: 3D reconstruction of brain hemisphere with labelled cells

Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

Shen Z et al. (2021) Cell Reports 34 (11): 108853.

DOI: 10.1016/j.celrep.2021.108853.

 

Highlights from the paper

  • Dorsal RGPs transition to gliogenesis progressively, with a peak at E16
  • Dorsal RGPs exhibit three gliogenic modes with well-defined probabilities
  • Intermediate precursors produce the same subtype of glia, forming local clusters
  • Clonal NF1 loss selectively enhances gliogenesis, especially the generation of OPCs

 

Summary from the paper

Radial glial progenitors (RGPs) give rise to the vast majority of neurons and glia in the neocortex. Although 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 behavior and gliogenesis program at single-cell resolution in the mouse neocortex. Fractions of dorsal RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of ∼60%, 15%, and 25%, respectively, by fate-restricted “intermediate” precursor cells (IPCs).

Although the total number of IPCs generated by individual RGPs appears stochastic, the output of individual IPCs 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 quantitatively delineate the cellular program of neocortical gliogenesis and suggest the cellular and lineage origin of primary brain tumor.

Simons Shen gliogenesis scheme 

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Read more about research in the Simons lab.

Watch Ben Simons describe his research in this short YouTube video.

 

 

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Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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