English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Human pluripotent stem cells (hPSCs) provide supplies of potential functional blood cells to suffice the clinical needs. However, the underlying mechanism of generating genuine hematopoietic stem cells (HSCs) and functional blood cells from hPSCs remains largely elusive.    Method  In this study, we supplied R-spondin2 exogenously during hematopoietic differentiation of hPSCs under various culture conditions and analyzed the production of hematopoietic progenitor cells (HPCs). We further added R-spondin2 at different temporal window to pin down the stage at which R-spondin2 conferred its effects. RNA-SEQ-based gene profiling was applied to analyze genes with significantly altered expression and altered signaling pathways. Finally, megakaryocytic differentiation and platelet generation were determined using HPCs with R-spondin2 treatment.    Results  We found that R-spondin2 generated by hematopoiesis-supporting stromal cells significantly enhances hematopoietic differentiation of hPSCs. Supply of R-spondin2 exogenously at the early stage of mesoderm differentiation elevates the generation of APLNR +  cells. Furthermore, early treatment of cells with R-spondin2 enables us to increase the output of hPSC-derived platelet-like particles (PLPs) with intact function. At the mechanistic level, R-spondin2 activates TGF-β signaling to promote the hematopoietic differentiation.    Conclusions  Our results demonstrate that a transient supply of R-spondin2 can efficiently promote hematopoietic development by activating both WNT and TGF-β signaling. R-spondin2 can be therefore used as a powerful tool for large-scale generation of functional hematopoietic progenitors and platelets for translational medicine.    Electronic supplementary material  The online version of this article (10.1186/s13287-019-1242-9) contains supplementary material, which is available to authorized users.

R-spondin2 promotes hematopoietic differentiation of human pluripotent stem cells by activating TGF beta signaling