Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells

Stem cells are of great interest to the scientific community due to their potential role in regenerative and rejuvenative medicine. However, their role in the aging process and carcinogenesis remains unclear. Because DNA replication in stem cells may contribute to the background mutation rate and thereby to cancer, reducing proliferation and establishing a relatively quiescent stem cell compartment has been hypothesized to limit DNA replication-associated mutagenesis. On the other hand, as the main function of stem cells is to provide daughter cells to build and maintain tissues, the idea of a quiescent stem cell compartment appears counterintuitive. Intriguing observations in mice have led to the idea of separated stem cell compartments that consist of cells with different proliferative activity. Some epithelia of short-lived rodents appear to lack quiescent stem cells. Comparing stem cells of different species and different organs (comparative stem cell biology) may allow us to elucidate the evolutionary pressures such as the balance between cancer and longevity that govern stem cell biology (evolutionary stem cell biology). The oral mucosa and its stem cells are an exciting model system to explore the characteristics of quiescent stem cells that have eluded biologists for decades.

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“…131 Also, in stem cells of acute myelogenous leukemia, Ring1 maintains the stemness of the cancer cells. 132…”

Section: Epigenetics Of Stemness and Quiescencementioning

confidence: 99%

Divide and conquer: two stem cell populations in squamous epithelia, reserves and the active duty forces

et al. 2019

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“…Here, we constructed a PPI network using nine colon CSC markers and discovered a cluster of significant targets. Most of these genes were related to CSCs, such as CD63 [45], MCM2 [46], CAV1 [47], GLIS2 [48], CDC20 [49,50], LATS2 [51] and FGF2 [52,53]. Interestingly, TMEM17, being the marker with the second highest resampling frequency in the survival analysis, has not been reported as marker of CSCs yet and its pathological function in other tumors has been found to be contradicted [19,20].…”

Section: Discussionmentioning

confidence: 99%

Protein–protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer

Chen

Zheng

et al. 2021

Cancer Cell Int

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Background Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with stem cell property. Increased evidence suggest that CSCs could be responsible for chemoresistance and recurrence in colorectal cancer (CRC). However, a reliable therapeutic target on CSCs is still lacking. Methods Here we describe a two-step strategy to generate CSC targets with high selectivity for colon stem cell markers, specific proteins that are interacted with CSC markers were selected and subsequently validated in a survival analysis. TMEM17 protein was found and its biological functions in CRC cells were further examined. Finally, we utilized the Gene Set Enrichment Analysis (GSEA) to investigate the potential mechanisms of TMEM17 in CRC. Results By combining protein–protein interaction (PPI) database and high-throughput gene profiles, network analysis revealed a cluster of colon CSCs related genes. In the cluster, TMEM17 was identified as a novel CSCs related gene. The results of in-vitro functional study demonstrated that TMEM17 depletion can suppress the proliferation of CRC cells and sensitize CRC cells to chemotherapy drugs. Enrichment analysis revealed that the expression of TMEM17 is associated with the magnitude of activation of the Wnt/β-catenin pathway. Further validation in clinical samples demonstrated that the TMEM17 expression was much higher in tumor than normal tissue and was associated with poor survival in CRC patients. Conclusion Collectively, our finding unveils the critical role of TMEM17 in CRC and TMEM17 could be a potential effective therapeutic target for tumor recurrence and chemoresistance in the colorectal cancer (CRC).

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“…30,31 A recent study reported that Glis2 promotes differentiation of AML stem cells in mice. 32 These results suggest that a change in GLIS2 regulation induces abnormal cell proliferation, leading to a risk of MM. We also found that the variants linked with the risks of most traits, specifically systemic sclerosis, were strongly enriched in binding motifs of EGR factors (EGR2, EGR3, and EGR4).…”

Section: Resultsmentioning

confidence: 88%

Functional variants in hematopoietic transcription factor footprints and their roles in the risk of immune system diseases

Kubota

Suyama

2021

Preprint

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Genome-wide association studies (GWAS) have been performed to identify thousands of variants in the human genome as disease risk markers, but functional variants that actually affect gene regulation and their genomic features remain largely unknown. Here we performed a comprehensive survey of functional variants in the regulatory elements of the human genome. We integrated hematopoietic transcription factor (TF) footprints datasets generated by ENCODE project with multiple quantitative trait locus (QTL) datasets (eQTL, caQTL, bQTL, and hQTL) and investigated the associations of functional variants and immune system disease risk. We identified candidate regulatory variants highly linked with GWAS lead variants and found that they were strongly enriched in active enhancers in hematopoietic cells, emphasizing the clinical relevance of enhancers in disease risk. Moreover, we found some strong relationships between traits and hematopoietic cell types or TFs. We highlighted some credible regulatory variants and found that a variant, rs2291668, which potentially functions in the molecular pathogenesis of multiple sclerosis, is located within a TF footprint present in a protein-coding exon of the TNFSF14 gene, indicating that protein-coding exons as well as noncoding regions can possess clinically relevant regulatory elements. Collectively, our results shed light on the molecular pathogenesis of immune system diseases. The methods described in this study can readily be applied to the study of the risk factors of other diseases.

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Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells

Cited by 19 publications

References 52 publications

Divide and conquer: two stem cell populations in squamous epithelia, reserves and the active duty forces

Divide and conquer: two stem cell populations in squamous epithelia, reserves and the active duty forces

Protein–protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer

Functional variants in hematopoietic transcription factor footprints and their roles in the risk of immune system diseases

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