Neural G0: a quiescent-like state found in neuroepithelial-derived cells and glioma

Abstract

In depth knowledge of the cellular states associated with normal and disease tissue homeostasis is critical for understanding disease etiology and uncovering therapeutic opportunities. Here, we used single cell RNA-seq to survey the cellular states of neuroepithelial-derived cells in cortical and neurogenic regions of developing and adult mammalian brain to compare with 38,474 cells obtained from 59 human gliomas, as well as pluripotent ESCs, endothelial cells, CD45+ immune cells, and non-CNS cancers.This analysis suggests that a significant portion of neuroepithelial-derived stem and progenitor cells and glioma cells that are not in G2/M or S phase exist in two states: G1 or Neural G0, defined by expression of certain neuro-developmental genes. In gliomas, higher overall Neural G0 gene expression is significantly associated with less aggressive gliomas, IDH1 mutation, and extended patient survival, while also anticorrelated with cell cycle gene expression. Knockout of genes associated with the Hippo/Yap and p53 pathways diminished Neural G0 in vitro, resulting in faster G1 transit, down regulation of quiescence-associated markers, and loss of Neural G0 gene expression. Thus, Neural G0 is a dynamic cellular state required for indolent cell cycles in neural-specified stem and progenitors poised for cell division. As a result, Neural G0 occupancy may be an important determinant of glioma tumor progression.

Single-cell Multi-omics reveal heterogeneity and metastasis potential in different liver cancer cell lines

“…The percent of G0 in each cell line was noted and in the cell lines with higher metastasis tended to have a lower percent of G0 cells which was consistent with previous studied that G0 cell populations are significantly associated with less aggressive tumors [65] . Similarly, having an increasing trend of amount of cell cycling cells had a higher metastatic potential which was consistent with a study in pancreatic ductal adenocarcinoma (PDAC) and increases in cell cycle progression in metastases might partly explain the high mortality in cancer.…”

Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease

“…The MITF-independent state that is shared between all disease conditions (cluster 1) maintains expression of neural crest markers sox10 and foxd3 with specific enrichment of erbb2 and zeb2a. Further, cluster 1 shows upregulation of ribosomal genes together with the cycle-cell inhibitor p27 (cdkn1bb) and arid1b, which together are enriched in a G 0 -like state (39). Notably, a few cells in cluster 1 strongly express the slow-cycling cell gene jarid1b (kdm5ba; ref.…”

Microenvironment Impacts the Molecular Architecture and Interactivity of Resident Cells in Marmoset Brain

“…Instead, cells expressing S and G2/M phase genes were dispersed within OPC1–3 subclusters. OPC4, however, was enriched with genes that defined as G0G1 (Figure 3B), i.e., quiescent cells (Feldman et al, 2019). Marmoset white matter OPC (OPC3) had lower transcriptomic agreement with OPC from other datasets than marmoset gray matter OPC (Figure 3I), supporting our speculation that white matter glia might be “older,” i.e., further deviated from their developmental status.…”