Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Hematopoietic development is spatiotemporally tightly regulated by defined cell-intrinsic and extrinsic modifiers. The role of cytokines has been intensively studied in adult hematopoiesis; however, their role in embryonic hematopoietic specification remains largely unexplored. Here, we used induced pluripotent stem cell (iPSC) technology and established a 3-dimensional, organoid-like differentiation system (hemanoid) maintaining the structural cellular integrity to evaluate the effect of cytokines on embryonic hematopoietic development. We show, that defined stages of early human hematopoietic development were recapitulated within the generated hemanoids. We identified KDR+/CD34high/CD144+/CD43-/CD45- hemato-endothelial progenitor cells (HEPs) forming organized, vasculature-like structures and giving rise to CD34low/CD144-/CD43+/CD45+ hematopoietic progenitor cells. We demonstrate that the endothelial to hematopoietic transition of HEPs is dependent on the presence of interleukin 3 (IL-3). Inhibition of IL-3 signalling blocked hematopoietic differentiation and arrested the cells in the HEP stage. Thus, our data suggest an important role for IL-3 in early human hematopoiesis by supporting the endothelial to hematopoietic transition of hemato-endothelial progenitor cells and highlight the potential of a hemanoid-based model to study human hematopoietic development.

Citation

Mania Ackermann, Kathrin Haake, Henning Kempf, Paul Kaschutnig, Anna-Carina Weiss, Ariane H H Nguyen, Markus Abeln, Sylvia Merkert, Mark Phillip Kühnel, Dorothee Hartmann, Danny Jonigk, Thomas Thum, Andreas Kispert, Michael D Milsom, Nico Lachmann. A 3D iPSC-differentiation model identifies interleukin-3 as a regulator of early human hematopoietic specification. Haematologica. 2021 May 01;106(5):1354-1367

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 32327499

View Full Text