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PROVIDER: PRJNA149983 | ENA |
REPOSITORIES: ENA
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Project description:Expression profiles of 7-day cultured HSPCs in the presence or absence of valproic acid and/or lithium. Two small molecules, valproic acid (VPA) and lithium (Li), were tested to inhibit differentiation of hematopoietic stem/progenitor (HSPC) cells in culture. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients and enhanced in vivo repopulating potential. Furthermore, VPA and Li synergistically preserved expression of stem cell-related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. Additionally, transcription factor networks were identified as possible primary regulators. Our results demonstrate that the combination of VPA and Li potently prevents differentiation at the biological and the molecular level, and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions. These data consist of total mRNA obtained from hematopoietic cells cultured for 7 days in the presence or absence of valproic acid and/or lithium. All samples were analyzed in independent biological triplicates.
2011-12-15 | E-GEOD-34088 | biostudies-arrayexpress
Project description:The combination of valproic acid and lithium delays hematopoietic stem\progenitor differentiation
2012-01-25 | GSE35292 | GEO
Project description:Two small molecules, valproic acid (VPA) and lithium (Li), were tested to inhibit differentiation of hematopoietic stem/progenitor (HSPC) cells in culture. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients and enhanced in vivo repopulating potential. Furthermore, VPA and Li synergistically preserved expression of stem cell-related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. Additionally, transcription factor networks were identified as possible primary regulators. Our results demonstrate that the combination of VPA and Li potently prevents differentiation at the biological and the molecular level, and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions. These data consist of total mRNA obtained from hematopoietic cells cultured for 7 days in the presence or absence of valproic acid and/or lithium. All samples were analyzed in independent biological triplicates.
2012-01-24 | E-GEOD-35291 | biostudies-arrayexpress
Project description:The combination of valproic acid and lithium delays hematopoietic stem\progenitor differentiation Microarray-based microRNA profiling study was peformed of four developmentally related hematopoietic cell types isolated from the BM of B6 and D2 mice. Total RNA isolated from purified LSK multilineage cells, committed LS−K+ cells, erythroid TER-119+ cells and myeloid Gr-1+ cells was hybridized to Single Color Illumina mouse WG-6_V2 mRNA arrays. Triplicates were generated for each of the 8 conditions (4 cell types, 2 mouse strains).
2012-01-25 | E-GEOD-35292 | biostudies-arrayexpress
Project description:Two small molecules, valproic acid (VPA) and lithium (Li), were tested to inhibit differentiation of hematopoietic stem/progenitor (HSPC) cells in culture. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients and enhanced in vivo repopulating potential. Furthermore, VPA and Li synergistically preserved expression of stem cell-related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. Additionally, transcription factor networks were identified as possible primary regulators. Our results demonstrate that the combination of VPA and Li potently prevents differentiation at the biological and the molecular level, and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions.
2012-01-24 | GSE35291 | GEO
Project description:The formation of hematopoietic cells relies on the chromatin remodeling activities of ISWI ATPase SMARCA5 (SNF2H) and its complexes. The Smarca5 null and conditional alleles have been used to study its functions in embryonic and organ development in mice. These mouse model phenotypes vary from embryonic lethality of constitutive knockout to less severe phenotypes observed in tissue-specific Smarca5 deletions, e.g., in the hematopoietic system. Here we show that, in a gene dosage-dependent manner, the hypomorphic allele of SMARCA5 (S5tg) can rescue not only the developmental arrest in hematopoiesis in the hCD2iCre model but also the lethal phenotypes associated with constitutive Smarca5 deletion or Vav1iCre-driven conditional knockout in hematopoietic progenitor cells. Interestingly, the latter model also provided evidence for the role of SMARCA5 expression level in hematopoietic stem cells, as the Vav1iCre S5tg animals accumulate stem and progenitor cells. Furthermore, their hematopoietic stem cells exhibited impaired lymphoid lineage entry and differentiation. This observation contrasts with the myeloid lineage which is developing without significant disturbances. Our findings indicate that animals with low expression of SMARCA5 exhibit normal embryonic development with altered lymphoid entry within the hematopoietic stem cell compartment.
2025-10-27 | PXD048865 | panorama
Project description:Analysis of the effects of valproic acid (VPA) on chronic myelogenous leukemia K562 cells. This study attempts to elucidate the effects of VPA on cell homeostasis and hematopoietic differentiation pathways in this cell line. We used ten experimental conditions comparing valproic acid-treated and untreated cells at time points 2, 6, 10, 48 and 72 hrs respectively. Experiments were performed in three biological replicates including a dye swap (represented by replicate 3, for each timepoint).
2010-12-01 | E-GEOD-19939 | biostudies-arrayexpress
Project description:Analysis of the effects of valproic acid (VPA) on chronic myelogenous leukemia K562 cells. This study attempts to elucidate the effects of VPA on cell homeostasis and hematopoietic differentiation pathways in this cell line.
2010-12-01 | GSE19939 | GEO
Project description:Expression profiles of LSK cells stimulated for 24h in the presence or in the absence of of valproic acid (VPA) The molecular process that underlies the biological effects of valproic acid (VPA), a widely used histone deacetylase inhibitor, on HSPCs was investigated by studying the early-response genes of VPA. Genome-wide gene expression studies revealed overrepresentation of genes involved in glutathione metabolism, receptor and signal transducer activity and changes in the HSPCs surface profile following short, 24h VPA treatment. Sca-1, a well-known and widely used stem cell surface marker, was identified as a prominent VPA target.VPA strongly preserved Sca-1 expression on LSK cells, but also re-activated Sca-1 on committed progenitor cells that were Sca-1 negative, thereby reverting them to the LSK phenotype. We demonstrated that re-acquired Sca-1 expression coincided with induced self-renewal capacity as measured by in vitro re-plating assays, while Sca-1 itself was not required for the biological effects of VPA as demonstrated using Sca-1 deficient progenitor cells. We show that VPA can induce several genes involved in signal transduction of which Sca-1 was shown to mark cells with increased self-renewal capacity. These data consist of total mRNA obtained from hematopoietic cells cultured for 24h in the presence or absence of valproic acid. All samples were analyzed in independent biological triplicates.
2012-09-25 | E-GEOD-41020 | biostudies-arrayexpress
Project description:In Vivo Chemical Screen Nominates Valproic Acid as Pharmacologic Modulator of Hematopoietic Stem and Progenitor Cell Activity
| PRJNA355003 | ENA