PROM1(CD133)-dependent expressed genes from mouse embryonic DRG neurons
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE147936 | GEO | 2020/04/02
REPOSITORIES: GEO
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Project description:PROM1(CD133)-dependent expressed genes from mouse embryonic DRG neurons
| PRJNA622574 | ENA
Project description:MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine 79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1 which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.
2020-03-25 | GSE135025 | GEO
Project description:MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine 79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1 which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.
2020-03-25 | GSE135024 | GEO
Project description:MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine 79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1 which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.
2020-03-25 | GSE135023 | GEO
Project description:As many other tumors, a subset of gliobastoma is thought to be maintained by a restricted population of cancer cells, stem-like cells that express CD133 transmembrane protein. Expression levels of CD133 gene has been linked to a poor prognostic molecular subgroup and is not overexpressed by the PDGF-driven proneural group. Thus, the significance of CD133+ cells for gliomagenesis of the proneural group is undetermined. In addition, the role of the CD133 protein remains elusive and controversial, which results from the difficult isolation of CD133+ cells that has largely relied on the use of antibodies to ill-defined glycosylated epitopes of CD133. Here, we used a knockin lacZ reporter mouse, Prom1lacZ/+, to track Prom1+ cells in the brain and found that Prom1 (prominin1, murine CD133 homologue) is expressed by cells that co-express markers characteristic of neuronal, glial and vascular lineage phenotype. In proneural tumors derived from injection of RCAS-PDGF into the brain of tv-a;Ink4a-Arf-/- Prom1lacZ/+ mice, Prom1+ cells co-express markers for astrocytes and endothelial cells. Therefore, we characterize the tumor propagation in a murine model and found that the mice co-transplanted with Prom1 endothelium and proneural tumor spheres cells had significant tumor burden and vascular proliferation (angiogenesis). Specific genes in Prom1 endothelium are identified that code for endothelial signaling modulators that most likely support proneural tumor progression and can be potential targets for anti-angiogenic therapy.
2013-12-31 | GSE43931 | GEO
Project description:As many other tumors, a subset of gliobastoma is thought to be maintained by a restricted population of cancer cells, stem-like cells that express CD133 transmembrane protein. Expression levels of CD133 gene has been linked to a poor prognostic molecular subgroup and is not overexpressed by the PDGF-driven proneural group. Thus, the significance of CD133+ cells for gliomagenesis of the proneural group is undetermined. In addition, the role of the CD133 protein remains elusive and controversial, which results from the difficult isolation of CD133+ cells that has largely relied on the use of antibodies to ill-defined glycosylated epitopes of CD133. Here, we used a knockin lacZ reporter mouse, Prom1lacZ/+, to track Prom1+ cells in the brain and found that Prom1 (prominin1, murine CD133 homologue) is expressed by cells that co-express markers characteristic of neuronal, glial and vascular lineage phenotype. In proneural tumors derived from injection of RCAS-PDGF into the brain of tv-a;Ink4a-Arf-/- Prom1lacZ/+ mice, Prom1+ cells co-express markers for astrocytes and endothelial cells. Therefore, we characterize the tumor propagation in a murine model and found that the mice co-transplanted with Prom1 endothelium and proneural tumor spheres cells had significant tumor burden and vascular proliferation (angiogenesis). Specific genes in Prom1 endothelium are identified that code for endothelial signaling modulators that most likely support proneural tumor progression and can be potential targets for anti-angiogenic therapy. Cells were sorted via FACS to obtain a population of CD31+CD133- cells and a population of CD31+CD133+ cells. Total RNA was extracted from each population and gene expression was assayed on Affymetrix Mouse 430 2.0 arrays with one array per cell population.
2013-12-31 | E-GEOD-43931 | biostudies-arrayexpress
Project description:Purpose: The function of Prom1, a penta-transmembrane glycoprotein which is a used as cancer stem cell marker, in the liver is unclear. The goal of this study is to examine the effect of Prom1 -/- in mouse primary hepatocyte transcriptomes. Prominin-1 (Prom1) is a major cell surface marker of cancer stem cells, but its physiological functions in the liver have not been elucidated. We analyzed the levels of mRNA transcripts in serum-starved primary Prom1+/+ and Prom1-/- mouse hepatocytes using RNA-sequencing (RNA-seq) data, and found that CREB target genes were down-regulated. This initial observation led us to determine that the Prom1 deficiency inhibited cAMP response element binding protein (CREB) activation and gluconeogenesis, but not cyclic AMP (cAMP) accumulation, in glucagon-, epinephrine-, or forskolin-treated liver tissues and primary hepatocytes, and mitigated glucagon-induced hyperglycemia. Because Prom1 interacted with radixin, the Prom1 deficiency prevented radixin from localizing to the plasma membrane. Moreover, systemic adenoviral knockdown of radixin inhibited CREB activation and gluconeogenesis in glucagon-treated liver tissues and primary hepatocytes, and mitigated glucagon-elicited hyperglycemia. Based on these results, we conclude that Prom1 regulates hepatic PKA signaling via radixin functioning as an A kinase-anchored protein (AKAP).
2020-01-22 | GSE144018 | GEO
Project description:CD133 has been widely used for identification and isolation of cancer stem cells in tumors although its role as a marker for cancer stem cell is still controversial . We isolated the CD133+ and CD133- cells from SW620 human colon cancer cell line and compared their biological characteristics, such as tumorigenicity,drug sensitivity, etc. Our study revealed that CD133+ SW620 cells were more tumorigenic and resistant to anti-cancer drugs. Correspondingly, they displayed different gene expression profile. However, it was observed that CD133- cells and CD133+ cells could mutually convert, indicating that CD133 expression was under dynamic and reversible regulations which might impose significant infulence on cells behaviors. Thus, our data challenge the role of CD133 as a marker for cancer stem cell.
2010-07-29 | GSE23295 | GEO
Project description:The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133- positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+CD140a- cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133+CD140a- NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+CD140a+ cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133+CD140a- cells. As human CD133+ cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain.
2013-04-23 | GSE40676 | GEO
Project description:The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133- positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+CD140a- cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133+CD140a- NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+CD140a+ cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133+CD140a- cells. As human CD133+ cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain. 12 samples, 4 groups (FACS-sorted cell populations),3 replicates in each group, each replicate is from a separate patient sample
2013-04-23 | E-GEOD-40676 | biostudies-arrayexpress