Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities [POLR1A]

ABSTRACT: A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities [POLR1A]

PROVIDER: PRJNA515613 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities [POLR1A]

Project description:Ribosomal RNA (rRNA) transcription and protein synthesis are heterogeneously regulated in colorectal tumors and are gradually shut down during cell differentiation. Cancer stem cell hierarchy and tumor growth is defined by a tumor cell population that displays elevated rRNA and protein synthesis.

2020-05-22 | GSE125231 | GEO

Zonation of ribosomal DNA transcription defines a stem cell hierarchy in colorectal cancer

Project description:Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occur in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA Polymerase 1 subunit A - POLR1A. Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest to CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5- tumor cells. Therefore, a common architecture in CRC is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins.

2020-04-09 | GSE148345 | GEO

A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities

Project description:A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities

| PRJNA515608 | ENA

A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities [EPHB2]

2020-05-22 | GSE125229 | GEO

A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities [EPHB2]

Project description:A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities [EPHB2]

| PRJNA515612 | ENA

Novel biallelic mutations in POLR1A: expansion of the phenotype and insight into the molecular mechanism

Project description:The eukaryotic genome is transcribed by three RNA polymerases (Pol) I, II and III; each transcribing different classes of RNAs. Pol I transcribes ribosomal DNA and produces the polycistronic rRNA 47S, which releases 28S, 18S and 5.8S rRNAs. Heterozygous mutations in the Pol I subunit POLR1A have been described in three patients presenting with Acrofacial Dysostosis, Cincinnati Type (MIM 616462), while a homozygous mutation in POLR1A was identified in two siblings, presenting developmental regression and several brain anomalies. We present three patients with homozygous mutations in POLR1A. Patient 1, a Norwegian male homozygous for POLR1A p.T642N, presented severe neurodegeneration with epilepsy, and died at 16 years of age. Patient 2, a 5.4-years-old Mexican male homozygous for POLR1A p.R667H, presented with severe neurodegeneration, epilepsy, and skeletal anomalies. Patient 3, a 2-year-old Dutch girl homozygous for POLR1A p.T642N, manifested severe global developmental delay, and brain anomalies. Structure superimposition of POLR1A wild-type and POLR1A T642N or R667H suggested a possible abnormal interaction between POLR1A and POLR2H. In vitro experiments showed that POLR1A T642N has higher transcriptional activity, abnormal rRNA processing, increased autophagy, deprotected telomeres, and reduced levels of p53. Proteomics analysis of patients 1 supported these findings, identifying dysfunction of pathways related to protein synthesis, ubiquitination, phagosome activities, and cell survival. In conclusion, we expand the phenotype of this rare disease and document a transcriptional defect affecting multiple processes, which impact cell survival.

2023-10-24 | PXD017431 | Pride

Heterozygous variants in POLR1A cause diverse human phenotypes

Project description:Heterozygous pathogenic variants in POLR1A were identified as the cause of Acrofacial Dysostosis, Cincinnati-type in 2015. Craniofacial anomalies reminiscent of Treacher Collins syndrome were the predominant phenotype observed in the first 3 affected individuals. We have subsequently identified 17 additional individuals with 12 unique (11 novel) heterozygous variants in POLR1A and observed numerous additional phenotypes including developmental delay, infantile spasms, and structural cardiac defects. To understand the pathogenesis of this pleiotropy, we created an allelic series of POLR1A using a combination of in vivo (mouse) and in vitro models. We describe distinct spatiotemporal requirements for Polr1a during mouse embryogenesis and identify a requirement for Polr1a for survival of pre migratory and migratory neural crest cells, forebrain precursors, and the second heart field. We used CRISPR/Cas9 to recapitulate two human alleles in mouse, demonstrating pathogenicity of one and likely benign nature of the other. Our work greatly expands the phenotype of human POLR1A-related disorders, provides new evidence of reduced penetrance and variable expression of POLR1A heterozygous variants, and demonstrates a multi-faceted approach to characterize and define pathogenicity of variants.

2022-08-15 | GSE206197 | GEO

A cancer stem cell hierarchy based on differential ribosomal RNA and protein synthesis capacities

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-22 | GSE125232 | GEO

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.

Project description:Identification and characterization of novel mechanisms driving melanoma metastases and ways to target them are paramount for the development of effective treatment modalities. We demonstrated that higher Polr1a levels correlate with increased metastasis and reduced survival in patients. In this study, we evaluated the effect of Polr1a knockdown on gene expression in melanoma cells.

2026-06-11 | GSE314397 | GEO

Zonation of ribosomal DNA transcription defines a stem cell hierarchy in colorectal cancer

Project description:Zonation of ribosomal DNA transcription defines a stem cell hierarchy in colorectal cancer

| PRJNA623941 | ENA