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Mitochondrial activity linked to CD34+CD90+EPCR+ phenotype determines the functional fitness of ex vivo expanded HSCs

ABSTRACT: We report the transcritpome of purified CD34+ cells from cultures initiated with cord blood CD34+ hematopoietic stem cells that were expanded ex vivo in Stemline II media supplemented with a cytokine cocktail in the presence or absence of valproic acid for 6 days .

ORGANISM(S): Homo sapiens

PROVIDER: GSE155180 | GEO | 2020/11/20

REPOSITORIES: GEO

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Mitochondrial activity linked to CD34+CD90+EPCR+ phenotype determines the functional fitness of ex vivo expanded HSCs

Project description:Mitochondrial activity linked to CD34+CD90+EPCR+ phenotype determines the functional fitness of ex vivo expanded HSCs

| PRJNA648928 | ENA

Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness of <i>ex vivo</i> Expanded Human Hematopoietic Stem Cells.

Project description:Ex vivo expansion strategies of human hematopoietic stem cell (HSC) grafts with suboptimal stem cell dose have emerged as promising strategies for improving outcomes of HSC transplantation in patients with hematological malignancies. While exposure of HSCs to ex vivo cultures expands the number of phenotypically identifiable HSCs, it frequently alters the transcriptomic and metabolic profiles, therefore, compromising their long-term (LT) hematopoietic reconstitution capacity. Within the heterogeneous pool of expanded HSCs, the precise phenotypic, transcriptomic and metabolic profile and thus, the identity of HSCs that confer LT repopulation potential remains poorly described. Utilizing valproic acid (VPA) in ex vivo cultures of umbilical cord blood (UCB)-CD34+ cells, we demonstrate that expanded HSCs phenotypically marked by expression of the stem cell markers CD34, CD90 and EPCR (CD201) are highly enriched for LT-HSCs. Furthermore, we report that low mitochondrial membrane potential, and, hence, mitochondrial activity distinguishes LT-HSCs within the expanded pool of phenotypically defined HSCs. Remarkably, such reduced mitochondrial activity is restricted to cells with the highest expression levels of CD34, CD90 and EPCR phenotypic markers. Together, our findings reveal that high expression of CD34, CD90 and EPCR in conjunction with low mitochondrial activity is critical for identification of functional LT-HSCs generated within ex vivo expansion cultures.

| S-EPMC7769876 | biostudies-literature

Expression data from untreated and valproic acid (VPA) treated CD34+ Hematopoietic Stem Cells (HSCs)

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.

2013-04-11 | GSE31283 | GEO

Expression data from untreated and valproic acid (VPA) treated CD34+ Hematopoietic Stem Cells (HSCs)

2013-04-11 | E-GEOD-31283 | biostudies-arrayexpress

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