Eupalinilide E Inhibits Erythropoiesis and Promotes the Expansion of Hematopoietic Progenitor Cells
2013; American Chemical Society; Volume: 8; Issue: 5 Linguagem: Inglês
10.1021/cb4000234
ISSN1554-8937
AutoresLorenzo de Lichtervelde, Anthony E. Boitano, Ying Wang, Philipp Krastel, Frank Petersen, Michael P. Cooke, Peter G. Schultz,
Tópico(s)Sphingolipid Metabolism and Signaling
ResumoHematopoietic 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.
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