Lack of lipid phosphate phosphatase‐3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth

Sánchez-Sánchez, Roberto; Morales‐Lázaro, Sara L.; Baizabal, José‐Manuel; Sunkara, Manjula; Morris, Andrew J.; Escalante‐Alcalde, Diana

doi:10.1002/dvdy.23779

Cited by 15 publications

(11 citation statements)

References 55 publications

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“…Study with LPP1 knockout mice indicated that LPP1 plays a role in regulating the degradation of circulating LPA in vivo but that study failed to disrupt the LPP1 encoding gene in the brain, obscuring the function of LPP1 in the nervous system [46]. Knockout of LPP3 turned out to be embryonically lethal [45] whereas in vitro studies using cell lines lacking LPP3 address involvement of LPP3 in early neural development [47]. The LPPs are likely to be involved in LPA dephosphorylation in brain cryosections, as brain sections efficiently generate P i from exogenous LPA largely in a NEM resistant and Mg 2+ -independent way.…”

Section: Discussionmentioning

confidence: 99%

Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

Eluwa¹,

Badru²,

Akpoigbe

2012

BMC Clin Pharmacol

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BackgroundData on adverse drug reactions (ADRs) related to antiretroviral (ARV) use in public health practice are few indicating the need for ART safety surveillance in clinical care.ObjectivesTo evaluate the incidence, type and risk factors associated with adverse drug reactions (ADRs) among patients on antiretroviral drugs (ARV).MethodsPatients initiated on ARVs between May 2006 and May 2009 were evaluated in a retrospective cohort analysis in three health facilities in Nigeria. Regimens prescribed include nucleoside backbone of zidovudine (AZT)/lamivudine (3TC), stavudine (d4T)/3TC, or tenofovir (TDF)/3TC in combination with either nevirapine (NVP) or efavirenz (EFV). Generalized Estimating Equation (GEE) model was used to identify risk factors associated with occurrence of ADR.Results2650 patients were followed-up for 2456 person-years and reported 114 ADRs (incidence rate = 4.6/100 person-years).There were more females 1706(64%) and 73(64%) of the ADRs were reported by women. Overall, 61(54%) of ADRs were reported by patients on AZT with 54(47%) of these occurring in patients on AZT/NVP. The commonest ADRs reported were pain 25(30%) and skinrash 10(18%). Most ADRs were grade 1(39%) with only 1% being life threatening (grade 4). Adjusted GEE analysis showed that ADR was less likely to occur in patients on longer duration of ART compared to the first six months on treatment; 6-12 months AOR 0.38(95% CI:0.16-0.91) and 12-24 months AOR 0.34(95% CI:0.16-0.73) respectively. Compared to patients on TDF, ADR was less likely to occur in patients on d4T and AZT AOR 0.18(95% CI 0.05-0.64) and AOR 0.24(95% CI:0.7-0.9) respectively. Age, gender and CD4 count were not significantly associated with ADRs.ConclusionADRs are more likely to occur within the first six months on treatment. Close monitoring within this period is required to prevent occurrence of severe ADR and improve ART adherence. Further research on the tolerability of tenofovir in this environment is recommended.

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Section: Discussionmentioning

confidence: 99%

Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

Eluwa¹,

Badru²,

Akpoigbe

2012

BMC Clin Pharmacol

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“…Arai et al (24) demonstrated that MSCs expressed ALCAM when involved in bone marrow formation. PPAP2B, which is a member of the phosphatidic acid phosphatase family, has been revealed to convert phosphatidic acid to diacylglycerol (25); and a previous study demonstrated that PPAP2B was involved in peroxisome proliferator-activated receptor-γ-induced osteoblastic cell differentiation in MSCs (26). Alison and Islam (27) revealed that miR-203 was involved in MSC differentiation by targeting several genes.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis on the differentiation of bone mesenchymal stem cells into osteoblasts and adipocytes

Liu

et al. 2017

Molecular Medicine Reports

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The present study aimed to screen several differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) for two types of mesenchymal stem cell (MSC) differentiation. Bone morphogenetic protein 6 (BMP-6) and dexamethasone were used to induce MSCs towards osteoblastic differentiation or adipocytic differentiation. The t-test in the Bioconductor bioinformatics software tool was used to screen DEGs and differentially expressed miRNAs in the two samples. Subsequent gene ontology (GO) and pathway analyses on the DEGs were performed using the GO and Kyoto Encyclopedia of Genes and Genomes databases, respectively; potential target genes for the screened miRNAs were predicted using the TargetScan database. In addition, an interaction network between the DEGs and miRNAs was constructed. Numerous DEGs and miRNAs were screened during osteoblastic and adipocytic differentiation of MSCs. Important pathways, such as glutathione metabolism, pathogenic Escherichia coli infection and Parkinson's disease, and GO terms, including cytoskeletal protein binding and phospholipase inhibitor activity, were enriched in the screened DEGs from MSCs undergoing osteogenic differentiation and adipocytic differentiation. miRNAs, including miRNA (miR)-382 and miR-203, and DEGs, including neuronal growth regulator 1 (NEGR1), phosphatidic acid phosphatase 2B (PPAP2B), platelet-derived growth factor receptor alpha (PDGFRA), interleukin 6 signal transducer (IL6ST) and sortilin 1 (SORT1), were demonstrated to be involved in osteoblastic differentiation. In addition, the downregulated miRNAs (including miR-495, miR-376a and miR-543), the upregulated miR-106a, the upregulated DEGs, including enabled homolog (ENAH), polypeptide N-acetylgalactosaminyltransferase 1 and acyl-CoA synthetase long-chain family member 1, and the downregulated repulsive guidance molecule family member B and semaphorin SEMA7A were demonstrated to be involved in adipocytic differentiation. The results of the present study suggested that miRNAs (miR-203 and miR-382) and DEGs (NEGR1, PPAP2B, PDGFRA, IL6ST and SORT1) may serve pivotal functions in the osteoblastic differentiation of MSCs, whereas miR-495, which is also involved in osteoblast differentiation and had four targets, including NEGR1, miR-376a, miR-543 and ENAH may have crucial roles in adipocytic differentiation of MSCs.

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“…Conversely, top downregulated genes in excitatory neurons (other than ribosomal and mitochondrial related genes), include many regulators of early stage neurogenesis (e.g. Slc1a3, Vcan, Tpi1, Vim, Lrrc17, Sox9 and Ppap2b) [84][85][86][87][88] . The contrasting natures of genes that are most downregulated in excitatory versus inhibitory neurons (neurogenesis vs neuron maturation), together with the opposite responses of the ribosomal and translational genes, which decrease with neuron differentiation 89 , may reveal a misalignment of developmental progress between these two major neuronal subtypes.…”

Section: Figurementioning

confidence: 99%

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

Donnard

Shu

Garber

2020

Preprint

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Despite advances in understanding the pathophysiology of Fragile X syndrome (FXS), its molecular bases are still poorly understood. Whole brain tissue expression profiles have proved surprisingly uninformative. We applied single cell RNA sequencing to profile a FXS mouse model. We found that FXS results in a highly cell type specific effect and it is strongest among different neuronal types. We detected a downregulation of mRNAs bound by FMRP and this effect is prominent in neurons. Metabolic pathways including translation are significantly upregulated across all cell types with the notable exception of excitatory neurons. These effects point to a potential difference in the activity of mTOR pathways, and together with other dysregulated pathways suggest an excitatory-inhibitory imbalance in the FXS cortex which is exacerbated by astrocytes. Our data demonstrate the cell-type specific complexity of FXS and provide a resource for interrogating the biological basis of this disorder.

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Lack of lipid phosphate phosphatase‐3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth

Cited by 15 publications

References 55 publications

Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

Bioinformatics analysis on the differentiation of bone mesenchymal stem cells into osteoblasts and adipocytes

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

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