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Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis

ABSTRACT: We explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number burst-forming units-erythroid (BFU-E), while lenalidomide specifically increased colony-forming units-erythroid (CFU-E). Use of the drugs in combination demonstrates that their effects are not redundant.

ORGANISM(S): Homo sapiens

PROVIDER: GSE28896 | GEO | 2011/04/28

SECONDARY ACCESSION(S): PRJNA140651

REPOSITORIES: GEO

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Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis

Project description:We explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number burst-forming units-erythroid (BFU-E), while lenalidomide specifically increased colony-forming units-erythroid (CFU-E). Use of the drugs in combination demonstrates that their effects are not redundant. Human CD34+ cells were cultured for 48 hours in the erythroid differentiation media described above with the addition of 40 ng/mL of FMS-like tyrosine kinase 3 (flt-3; Miltenyi Biotech) and 15 ng/mL of Granulocyte colony-stimulating factor (G-CSF; Amgen). Cells were cultured in the presence of the drugs of interest for 24 hours. RNA was purified using Trizol (Invitrogen). RNA was amplified and labeled by in vitro transcription and hybridized to the Affymetrix HT Human Genome U133A Array. Three replicates per condition.

2011-04-28 | E-GEOD-28896 | biostudies-arrayexpress

Isolation and Transcriptome Analyses of Human Erythroid Progenitors: BFU-E and CFU-E

Project description:Burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) cells are erythroid progenitors traditionally defined by colony assays. We developed a flow cytometry-based strategy for isolating human BFU-E and CFU-E cells based on the changes in expression of cell surface markers during in vitro erythroid cell culture. BFU-E and CFU-E are characterized by CD45+GPA-IL-3R-CD34+CD36-CD71low and CD45+GPA-IL-3R-CD34-CD36+CD71high phenotypes, respectively. Colony assays validated phenotypic assignment giving rise to BFU-E and CFU-E colonies, both at a purity ~90%. The BFU-E colony forming ability of CD45+GPA-IL-3R-CD34+CD36-CD71low cells required SCF and erythropoietin, while the CFU-E colony forming ability of CD45+GPA-IL-3R-CD34-CD36+CD71high cells required only erythropoietin. Bioinformatic analysis of the RNA-seq data revealed unique transcriptomes in each differentiation stage. The sorting strategy was validated in uncultured primary cells isolated from bone marrow and peripheral blood, indicating that marker expression is not an artifact of in vitro cell culture, but represents an in vivo characteristic of erythroid progenitor populations. The ability to isolate highly pure human BFU-E and CFU-E progenitors will enable detailed cellular and molecular characterization of these distinct progenitor populations and define their contribution to disordered erythropoiesis in inherited and acquired hematological disease. Our data provide important resource for future studies. Transcription profiles of Human erythroid progenitors at distinct developmental stages were generated by deep sequencing, in triplicate, using IlluminaHiSeq 2000. The complete dataset comprises 4 sample types: CD34, BFU, CFU, and Pro (reanalysis of GSM1304777-GSM1304779).

2014-10-30 | E-GEOD-61566 | biostudies-arrayexpress

Isolation and Transcriptome Analyses of Human Erythroid Progenitors: BFU-E and CFU-E

2014-10-30 | GSE61566 | GEO

Synergism between PPAR? and glucocorticoid receptor signaling promotes self-renewal of BFU-E erythroid progenitors and increases red cell production [RNA-seq]

Project description:Analyses of gene expression by RNA-Seq in mouse E14.5 fetal liver burst-forming unit erythroid (BFU-E) cells untreated or treated by dexamethasone (DEX) with or without PPAR? agonist GW7647. RNA-Seq was performed on enriched populations of mouse BFU-E isolated from E14.5 fetal liver, as well as BFU-E enriched cells treated with Dex ± GW7647.

2015-06-08 | E-GEOD-63836 | biostudies-arrayexpress

Single cell RNA sequencing of primary-isolated erythroid progenitors [Days 1-3]

Project description:single cell RNA sequencing of freshly isolated mouse BFU-E (burst forming unit-erythroid ) cells cultured for 1, 2, or 3 days with and without 100nM dexamethasone

2019-03-01 | GSE117231 | GEO

Synergism between PPARα and glucocorticoid receptor signaling promotes self-renewal of BFU-E erythroid progenitors and increases red cell production [RNA-seq]

2015-06-08 | GSE63836 | GEO

Single cell RNA sequencing of primary-isolated erythroid progenitors [BFUE & CFUE]

Project description:single cell RNA sequencing of freshly isolated mouse burst forming unit-erythroid (BFU-E) and colony forming unit-erythroid (CFU-E).

2019-03-01 | GSE117225 | GEO

Single cell RNA sequencing of primary-isolated erythroid progenitors [BFUE, CFUE, intermediates]

Project description:Single cell RNA sequencing of freshly isolated mouse burst forming unit-erythroid (BFU-E) , colony forming unit-erythroid (CFU-E), and intermediate stages of erythroid development cells.

2019-03-01 | GSE117228 | GEO

Single cell RNA sequencing of primary-isolated erythroid progenitors [daughter cells]

Project description:Single cell mouse BFU-E (burst forming unit-erythroid ) were FACS-deposited into individual wells of a 96-well plate containing PCM either with or without 100 nM dexamethasone. After 16hrs cells from wells that contained a single pair of daughter cells were separated and each individual daughter cell transcriptome was obtained by single cell RNA-seq.

2019-03-01 | GSE117232 | GEO

Single cell RNA sequencing of primary-isolated erythroid progenitors [BFUEs_Set2]

Project description:Single cell RNA sequencing of freshly isolated mouse burst forming unit-erythroid (BFU-E).

2019-03-01 | GSE127454 | GEO