title: Eupalinilide E inhibits erythropoiesis and promotes the expansion of hematopoietic progenitor cells.
abstract: Hematopoietic stem cells (HSCs) are the progenitor cells that give rise to all blood cells. The ability to control HSC differentiation has the potential to improve the success of bone marrow transplants and the production of functional blood cells ex vivo. Here we performed an unbiased screen using primary human CD34(+) hematopoietic stem and progenitor cells (HSPCs) to identify natural products that selectively control their differentiation. We identified a plant-derived natural product, eupalinilide E, that promotes the ex vivo expansion of HSPCs and hinders the in vitro development of erythrocytes. This activity was additive with aryl hydrocarbon receptor (AhR) antagonists, which are also known to expand HSCs and currently in clinical development. These findings reveal a new activity for eupalinilide E, and suggest that it may be a useful tool to probe the mechanisms of hematopoiesis and improve the ex vivo production of progenitors for therapeutic purposes.
authors: Lorenzo
authors: L
authors: de Lichtervelde
authors: Anthony E
authors: AE
authors: Boitano
authors: Ying
authors: Y
authors: Wang
authors: Philipp
authors: P
authors: Krastel
authors: Frank
authors: F
authors: Petersen
authors: Michael P
authors: MP
authors: Cooke
authors: Peter G
authors: PG
authors: Schultz
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay / Q000379:methods; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors; D011990:Receptors, Transferrin / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; C068126:CD71 antigen; D003470:Culture Media; D004147:Dioxins; D016328:NF-kappa B; D018336:Receptors, Aryl Hydrocarbon; D011990:Receptors, Transferrin; D012717:Sesquiterpenes; C585894:eupalinilide E