Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells.

Autor: Chang Y; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA., Syahirah R; Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA., Oprescu SN; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA; Department of Animal Sciences, Purdue University, West Lafayette, IN, 47907, USA., Wang X; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Jung J; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA., Cooper SH; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Torregrosa-Allen S; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA., Elzey BD; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA., Hsu AY; Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA; Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA., Randolph LN; Departments of Biomedical Engineering, Biology, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA., Sun Y; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA., Kuang S; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA; Department of Animal Sciences, Purdue University, West Lafayette, IN, 47907, USA., Broxmeyer HE; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Deng Q; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA; Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA. Electronic address: qingdeng@purdue.edu., Lian X; Departments of Biomedical Engineering, Biology, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA. Electronic address: Lian@psu.edu., Bao X; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA. Electronic address: bao61@purdue.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2022 Jun; Vol. 285, pp. 121569. Date of Electronic Publication: 2022 May 06.
DOI: 10.1016/j.biomaterials.2022.121569
Abstrakt: Human hematopoietic stem cells (HSCs), which arise from aorta-gonad-mesonephros (AGM), are widely used to treat blood diseases and cancers. However, a technique for their robust generation in vitro is still missing. Here we show temporal manipulation of Wnt signaling is sufficient and essential to induce AGM-like hematopoiesis from human pluripotent stem cells. TGFβ inhibition at the stage of aorta-like SOX17 + CD235a - hemogenic endothelium yielded AGM-like hematopoietic progenitors, which closely resembled primary cord blood HSCs at the transcriptional level and contained diverse lineage-primed progenitor populations via single cell RNA-sequencing analysis. Notably, the resulting definitive cells presented lymphoid and myeloid potential in vitro; and could home to a definitive hematopoietic site in zebrafish and rescue bloodless zebrafish after transplantation. Engraftment and multilineage repopulating activities were also observed in mouse recipients. Together, our work provided a chemically-defined and feeder-free culture platform for scalable generation of AGM-like hematopoietic progenitor cells, leading to enhanced production of functional blood and immune cells for various therapeutic applications.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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