PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth
Cleveland, A. H.; Malawsky, D.; Churiwal, M.; Rodriguez, C.; Reed, F.; Schniederjan, M.; Velazquez Vega, J. E.; Davis, I.; Gershon, T. R.
Show abstract
We show that the Polycomb Repressive Complex 2 (PRC2) maintains neural identity in Sonic Hedgehog (SHH)-driven cerebellar granule neuron progenitors (CGNPs) and SHH-driven medulloblastoma, a cancer of CGNPs. Proliferating CGNPs and medulloblastoma cells pass the neural fate commitment to their progeny through epigenetic mechanisms. The PRC2 mediates epigenetic regulation through histone methylation, and PRC2 inhibitors have been proposed for medulloblastoma therapy. We investigated PRC2 function in CGNPs and medulloblastoma by conditionally deleting PRC2 components Eed or Ezh2 in CGNPs and analyzing cerebellar growth, cellular gene expression (scRNA-seq), and tumorigenesis in medulloblastoma-prone Smo-mutant mice. Eed-deleted CGNPs showed reduced growth, with decreased proliferation, increased apoptosis and inappropriate myoid differentiation. Ezh2-deleted CGNPs also showed myoid differentiation without reduced growth. Eed-deleted and Ezh2-deleted medulloblastomas similarly demonstrated myoid differentiation, but progressed more rapidly than PRC2-intact controls. The PRC2 thus maintained neural fate in CGNPs and medulloblastoma, but PRC2 disruption did not block SHH medulloblastoma progression.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Aberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma 96%
- Transcriptional regulation of neural stem cell expansion in adult hippocampus 95%
- A novel, ataxic mouse model of Ataxia Telangiectasia caused by a clinically relevant nonsense mutation 94%
Similar papers in this journal
- Multifaceted functions of Rab23 on primary cilium and Hedgehog signaling-mediated granule cell proliferation 95%
- HIFα regulates developmental myelination independent of autocrine Wnt signaling 94%
- The neocortical progenitor specification program is established throughcombined modulation of SHH and FGF signaling 94%
Similar papers in this journal
- Siah2 integrates mitogenic and extracellular matrix signalslinking neuronal progenitor ciliogenesis with germinal zoneoccupancy. 96%
- Endosomal trafficking defects alter neural progenitor proliferation and cause microcephaly 94%
- Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways 94%
Similar papers in this journal
- The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance and neuronal survival in mice 95%
- Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics. 94%
- An evolutionarily acquired microRNA shapes development of mammalian cortical projections 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.