RHOB regulates megakaryocytes and erythroid differentiation by altering the cell cycle and cytoskeleton.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1187594 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31384625_1.fastq.gz | Fastqsanger.gz | |||
| SRR31384625_2.fastq.gz | Fastqsanger.gz | |||
| SRR31384626_1.fastq.gz | Fastqsanger.gz | |||
| SRR31384626_2.fastq.gz | Fastqsanger.gz | |||
| SRR31384627_1.fastq.gz | Fastqsanger.gz |
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Project description:RHOB, a member of the Rho GTPase family, is a target of miR-1915-3p. miR-1915-3p has been proved by us to affect the differentiation of MEPs, promoting the differentiation of megakaryocytes and inhibiting the erythroid lineage, which may lead to an increase in the number of platelets and a decrease in the number of erythrocytes. Although RHOB has been confirmed to be involved in the process of proplatelets production in mice, its role in early hematopoietic differentiation, especially its impact on the megakaryocytic and erythroid differentiation of human HSCs and MEPs, has not yet been elucidated. In this study, we confirmed that the function of the RHOB gene was opposite to miR-1915-3p by knocking down the gene in progenitor cells and inducing them into different cells. Silencing of RHOB significantly decreased the erythroid surface markers, reduced the diameter of the cell and inhibited the expression of erythroid-related genes in human cells. Furthermore, RHOB knockdown in megakaryocytic-induced cells increased the megakaryocytic surface markers, enlarged cell and nuclear volume and promoted cell polyploidy and megakaryocyte-related gene expression. The results of RNA sequencing suggest that the RHOB may play a role in differentiation by influencing the cell cycle and the cytoskeleton. Based on that, we found RHOB could affect the expression of differential CDKs and cyclins to alter the proportions of G0/1 and S phase cells and influent the expression or aggregation of β-ACTIN during erythroid or megakaryocytic differentiation. Taken together, these results suggest that RHOB plays an important role in megakaryocytic and erythroid differentiation by cell cycle and cytoskeleton regulation.
2025-04-23 | GSE282217 | GEO
Project description:Purpose: RhoB regulates cell functions, such as vesicular transport, apoptosis, autophagy, DNA repair, angiogenesis, proliferation, migration and invasion. We investigated whether RhoB is involved in the pathogenesis of ulcerative colitis (UC).We performed RNA sequencing analysis in intestinal epithelial cells (IECs) from RhoB-deficient mice and WT mice to study the molecular mechanisms through which RhoB regulates goblet cell numbers and epithelial regeneration and confirmed findings in colonic organoids from RhoB-deficient mice and WT mice and siRhoB transfected SW480 cells.
2022-09-27 | GSE170994 | GEO
Project description:RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We used microarrays to link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to RhoB/VEZF1-mediated gene regulation in primary human blood versus lymphatic endothelial cells.
2013-10-28 | GSE51754 | GEO
Project description:Activation of the PI3K/Akt/mTOR pathway in cancers can occur through loss of PTEN. Transcriptional profiling of pathway inhibitors identified the tumor suppressor RhoB as a gene markedly upregulated by lipid-based Akt inhibitors (LBAI). Here, we demonstrate that the C/EBPbeta full-length isoform LAP is responsible for transcriptional induction through its binding site within the RhoB proximal promoter. LBAI strongly transactivate RhoB by switching translation of C/EBPbeta from the truncated isoform LIP to LAP via PACT-mediated PKR activation in cancer cells with high Akt activity. Unlike PTEN commonly mutated, endogenous RhoB tumor-suppressive activity can be reconstituted by restoring its expression, which was noninvasively monitored by a RhoB promoter-driven luciferase reporter in living mice. LBAI administration increased luciferase activity and decreased the growth of human tumor xenografts. Increased PKR activation by LBAI leads to more robust RhoB induction and cytotoxicity than other PI3K/Akt/mTOR axis inhibitors, revealing a novel strategy for cancer therapy.
2015-01-29 | GSE28993 | GEO
Project description:RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We used microarrays to link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to RhoB/VEZF1-mediated gene regulation in primary human blood versus lymphatic endothelial cells. Pure populations of human primary BVECs and LVECs silenced for RhoB or VEZF1 were used for RNA extraction and hybridization on Affymetrix microarrays. We extracted these cells from human male foreskins from at least four individuals and purified them using Dynabeads associated with vascular markers (CD31 and Podoplanin).
2013-10-28 | E-GEOD-51754 | biostudies-arrayexpress
Project description:Rationale: Endothelial cells (ECs) line the inner surface of continuous capillaries and form a permselective barrier between blood and tissues to limit paracellular fluid and solute flux. The capillary barrier is maintained by intercellular tight junctions (TJs) which are regulated, in part, by differential activity of small GTPases. Tumor necrosis factor (TNF) causes TJ disassembly in a process dependent upon NF-κB-mediated gene expression. Activated (GTP-bound) RhoB has been identified as a downstream effector of TNF-induced leak both through Rho-associated coiled-coil kinase-mediated phosphorylation of RelA, enhancing TNF-induced NF-κB-mediated gene activation, and through sequestration of Rac1 away from the cell junction, preventing barrier restoration. To date, no TNF-induced, RhoB-selective GTP exchange factor (GEF) has been identified in ECs. Objective: Identify a TNF-induced RhoB specific GEF in capillary ECs. Method and Results: human dermal microvascular ECs (HDMECs) were used because they form TJs. Candidate GEFs were identified by whole transcriptome profiling of HDMECs with or without TNF stimulation. Fifty-seven of 73 known GEFs were expressed in HDMECs and 17 were significantly upregulated by TNF. Functional impact of each of the latter group was assessed by measuring the effects of depletion by short interfering RNA knockdown on TNF-induced reduction of trans-endothelial electrical resistance (TEER) of HDMEC monolayers. Depletions of ArhGEF10 or RhoB or double depletion of ArhGEF10/RhoB similarly decreased TNF-mediated reduction of TEER. ArhGEF10 knockdown prevented TNF-induced disruption of TJ proteins assessed by confocal microscopy. TNF-induced increases in the levels of activated RhoB in HDMEC lysates were markedly reduced with only minimal alterations in RhoA or RhoC activation. Finally, immunoisolated ArhGEF10 selectively catalyzed GTP exchange for GDP in RhoB, but not RhoA or RhoC, in vitro. Conclusion: ArhGEF10 is a TNF-induced RhoB-selective GEF for RhoB in cultured human capillary ECs that contributes to TJ disruption.
2021-05-10 | GSE161021 | GEO
Project description:Endometriosis is a common disease in women characterized by the growth of endometrial-like lesions at ectopic sites, associated with chronic pelvic pain and infertility. LINC01638 is a long non-coding RNA (lncRNA) that in several cancers has been implicated in the regulation of proliferation and epithelial-to-mesenchymal transition (EMT). Given that these processes are also important in endometriosis, we investigated the role of LINC01638 in this disease. We found that LINC01638 is upregulated in the epithelial layer of endometriosis lesions, and that knockdown of the gene in 12Z epithelial endometriosis cell line led to reduced proliferation, adhesion, migration and invasion. The reduction in proliferation was associated with increased p21 and p27 expression and G1 phase arrest of 12Z cells, showing that LINC01638 acts as an important epigenetic regulator of endometriosis epithelial cells cell cycle progression. Further, transcriptome analysis of LINC01638 control and knockdown cells revealed that a number of transcription factors associated with EMT are downregulated in the knockdown, including FOXC2, SNAI2, TWIST1 and ZEB1, along with the mesenchymal marker VIM. These genetic and phenotypic changes in 12Z knockdown cells were accompanied by a significant reduction in expression of cytoskeleton regulatory gene RHOB and an upregulation of HDAC1 expression. Chromatin immunoprecipitation analysis and HDAC1 inhibitory treatment in LINC01638 control and knockdown cells indicated that LINC01638 regulates RHOB expression via HDAC1 mediated regulation of its promoter acetylation. In vivo, RHOB is upregulated in the epithelial layer of endometriosis lesions compared to control and endometriosis patient eutopic endometrium, supporting a role in the disease. Together these results indicate that LINC01638 is an epigenetic regulator of pathogenesis of endometriosis promoting proliferation and EMT of endometriosis lesions.
2025-02-16 | GSE281916 | GEO
Project description:Primary adult peripheral blood (PB) megakaryocytes and umbilical cord blood (CB) megakaryocytes
2024-05-10 | GSE264384 | GEO
Project description:Cord blood CD34+ hematopoietic precursors (3 donors) were control or HES6 shRNA (HES6 knockdown) transduced and cultured for four days in media containing SCF, TPO and EPO to drive differentiation towards megakaryocytes and erythroid cells. After four days four subpopulations were sorted for RNA isolation to research the effect of HES6 knockdown on gene expression. We sorted megakaryocytes (CD41+) and early (CD71+ CD235-) and late (CD71+ CD235+) erythroblasts (CD41-) and CD34- precursor cells (CD41- CD71- CD235- CD34-).
2024-11-13 | GSE229196 | GEO
Project description:Activation of the PI3K/Akt/mTOR pathway in cancers can occur through loss of PTEN. Transcriptional profiling of pathway inhibitors identified the tumor suppressor RhoB as a gene markedly upregulated by lipid-based Akt inhibitors (LBAI). Here, we demonstrate that the C/EBPbeta full-length isoform LAP is responsible for transcriptional induction through its binding site within the RhoB proximal promoter. LBAI strongly transactivate RhoB by switching translation of C/EBPbeta from the truncated isoform LIP to LAP via PACT-mediated PKR activation in cancer cells with high Akt activity. Unlike PTEN commonly mutated, endogenous RhoB tumor-suppressive activity can be reconstituted by restoring its expression, which was noninvasively monitored by a RhoB promoter-driven luciferase reporter in living mice. LBAI administration increased luciferase activity and decreased the growth of human tumor xenografts. Increased PKR activation by LBAI leads to more robust RhoB induction and cytotoxicity than other PI3K/Akt/mTOR axis inhibitors, revealing a novel strategy for cancer therapy. H157 cells were plated 2 x 10^6 in T-75 flasks in RPMI 1640 containing 10% FBS and incubated for 24h. The medium was then changed to RPMI 1640 with 0.1% FBS and the cells were incubated overnight. The following morning, cells were treated with 10 microM of LY294002, OSU03012, PIA23, Perifosine, Miltefosine, API-2, DZ-50, or 100 nM of Wortmannin and Rapamycin for 6 hours, or an equal amount of DMSO as control. Following incubation, total RNA was extracted from cells in T-75 flasks using TRIzol reagent (Invitrogen). Two dye-swapped replicates were performed for each treatment.
2015-01-29 | E-GEOD-28993 | biostudies-arrayexpress