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bioRxiv · 10.1101/2024.08.07.606990

Canonical and non-canonical PRC1 differentially contribute to the regulation of neural stem cell fate

Hoffmann, J.·Schutze, T. M.·Kolodziejczyk, A.·Krankel, A.·Reinhardt, S.·Derihaci, R. P.·Birdir, C.·Wimberger, P.·Koseki, H.·Albert, M.
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Abstract

Neocortex development is characterized by sequential phases of neural progenitor cell (NPC) expansion, neurogenesis and gliogenesis. Polycomb-mediated epigenetic mechanisms are known to play important roles in regulating the lineage potential of NPCs during development. The composition of Polycomb Repressive Complex 1 (PRC1) is highly diverse in mammals and was hypothesized to contribute to context-specific regulation of cell fate. Here, we have performed side-by-side comparison of the role of canonical PRC1.2/1.4 and non-canonical PRC1.3/1.5, all of which are expressed in the developing neocortex, in NSC proliferation and differentiation. We found that the deletion of Pcgf2/4 in NSCs led to a strong reduction in proliferation and to altered lineage fate, both during the neurogenic and gliogenic phase, whereas Pcgf3/5 played a minor role. Mechanistically, genes encoding stem cell and neurogenic factors were bound by PRC1 and differentially expressed upon Pcgf2/4 deletion. Thus, rather than different PRC1 sub-complexes contributing to different phases of neural development, we found that canonical PRC1 played a more significant role in NSC regulation during proliferative, neurogenic and gliogenic phases compared to non-canonical PRC1.

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Hoffmann, J., Schutze, T. M., Kolodziejczyk, A., Krankel, A., Reinhardt, S., Derihaci, R. P., Birdir, C., Wimberger, P., Koseki, H., Albert, M.. 2024-08-07. Canonical and non-canonical PRC1 differentially contribute to the regulation of neural stem cell fate. https://doi.org/10.1101/2024.08.07.606990

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