کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2093228 | 1081947 | 2016 | 12 صفحه PDF | دانلود رایگان |
• cAMP induction increases HSC-like cell generation from human pluripotent stem cells
• cAMP signaling through Epac axis modulates hemogenic endothelium
• cAMP upregulates anti-oxidative mechanisms and creates redox-state balance
• cAMP induction enhances CXCR4 expression in hematopoietic progenitors
SummaryHematopoietic cells emerge from hemogenic endothelium in the developing embryo. Mechanisms behind human hematopoietic stem and progenitor cell development remain unclear. Using a human pluripotent stem cell differentiation model, we report that cyclic AMP (cAMP) induction dramatically increases HSC-like cell frequencies. We show that hematopoietic cell generation requires cAMP signaling through the Exchange proteins activated by cAMP (cAMP-Epac) axis; Epac signaling inhibition decreased both hemogenic and non-hemogenic endothelium, and abrogated hematopoietic cell generation. Furthermore, in hematopoietic progenitor and stem-like cells, cAMP induction mitigated oxidative stress, created a redox-state balance, and enhanced C-X-C chemokine receptor type 4 (CXCR4) expression, benefiting the maintenance of these primitive cells. Collectively, our study provides insights and mechanistic details on the previously unrecognized role of cAMP signaling in regulating human hematopoietic development. These findings advance the mechanistic understanding of hematopoietic development toward the development of transplantable human hematopoietic cells for therapeutic needs.
Graphical AbstractFigure optionsDownload as PowerPoint slide
Journal: - Volume 6, Issue 5, 10 May 2016, Pages 692–703