类有机物
诱导多能干细胞
造血
祖细胞
细胞生物学
干细胞
生物
间充质干细胞
内皮干细胞
骨髓
成体干细胞
造血干细胞
胚胎干细胞
免疫学
体外
基因
遗传学
作者
Stephanie Frenz-Wiessner,Savannah Fairley,Maximilian Buser,Isabel Goek,Kirill Salewskij,Gustav Jonsson,David W. 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 Penninger,Carsten Marr,Christoph Klein
标识
DOI:10.1038/s41592-024-02172-2
摘要
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.
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