CD34+ HSPC CITE-seq for day 0 and Day 1 and Day 4 under VPA
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ABSTRACT:
PROVIDER: PRJNA903209 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22341900_1.fastq.gz | Fastqsanger.gz | |||
| SRR22341900_2.fastq.gz | Fastqsanger.gz | |||
| SRR22341901_1.fastq.gz | Fastqsanger.gz | |||
| SRR22341901_2.fastq.gz | Fastqsanger.gz | |||
| SRR22341902_1.fastq.gz | Fastqsanger.gz |
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Project description:Histone deacetylase (HDAC) inhibitors are widely utilized in hematopoietic malignance therapy; nevertheless, little is currently known concerning their effects on normal myelopoiesis. In order to investigate a putative interference of HDAC inhibitors in myeloid commitment of hematopoietic stem/progenitor cells (HSPCs) we treated CD34+ cells with valproic acid (VPA). Moreover, we investigate changes in gene expression induced by VPA treatment on HSPCs, by means of microarray analysis in VPA treated and untreated (CTR) CD34+ cells. VPA treatment induced H4 histone acetylation in CD34+ cells and blocked them in G0-G1 phase of cell cycle. CD34 expression is maintained for a longer time in VPA treated cells, while the physiological decrease of CD34 antigen occurred in CTR cells. Moreover, VPA favored erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage lineages, as demonstrated by immunophenotyping, morphological and clonogenic analysis. Finally, we demonstrated that VPA up-regulated master gene regulators of erythrocyte and megakaryocyte differentiation (GFI1B and MLLT3) through histone iper-acetylation of their promoters. These results indicate that VPA treatment enhances erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage one. Microarray data provide for the first time a detailed molecular support for the biological effects promoted by VPA treatment in HSPCs. Human CD34+ cells were purified from umbilical Cord Blood (CB) samples. After an initial 24 hours of incubation, CD34+ cells were exposed to VPA. Total cellular RNA was extracted from untreated (CTR) and VPA treated CD34+ HSCs after 48 hours of treatment.
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