Generation of complex human induced pluripotent stem cell-derived bone marrow organoids

Stephanie Frenz-Wiessner, Savannah D. Fairley, Maximilian Buser, Isabel Goek, Kirill Salewskij, Gustav Jonsson, David Illig, Benedicta zu Putlitz, Daniel Petersheim, Yue Li, Pin-Hsuan Chen, Martina Kalauz, Raffaele Conca, Michael Sterr, Johanna Geuder, Yoko Mizoguchi, Remco T. A. Megens, Monika I. Linder, Daniel Kotlarz, Martina Rudelius, Josef M. Penninger, Carsten Marr, Christoph Klein

Abstract

The human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.

Datasets

1. Bone marrow organoids (BMO)
Metadata
bmo
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BMO 28746 cells
BMO 57244 cells
BMO 46081 cells
BMO 34686 cells
BMO 14283 cells
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Generation of complex human induced pluripotent stem cell-derived bone marrow organoids

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Source data

https://cellxgene.cziscience.com/collections/59cd85c5-3b22-4035-b628-2a20810ad54b

Alias names

GSE249005, PMID38374263, PMC11093744

Cite this study

Frenz, S., Goek, I., Buser, M., Salewskij, K., Fairley, S., Conca, R., Drexler, N., Jonsson, G., Thomas, M., Mizoguchi, Y. and Rudelius, M., 2022. Generation of Human Induced Pluripotent Stem Cell-Derived Bone Marrow Organoids. Blood, 140(Supplement 1), pp.1682-1683. https://doi.org/10.1038/s41592-024-02172-2