Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells. (June 2022)

• Record Type: Journal Article
• Authors: Chang, Yun; Syahirah, Ramizah; Oprescu, Stephanie N.; Wang, Xuepeng; Jung, Juhyung; Cooper, Scott H.; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Hsu, Alan Y.; Randolph, Lauren N.; Sun, Yufei; Kuang, Shihuan; Broxmeyer, Hal E.; Deng, Qing; Lian, Xiaojun; Bao, Xiaoping
• Is Part Of: Biomaterials. Volume 285(2022)
• Publication Date: 2022-06
• Subjects: Stem cell differentiation -- Hematopoietic stem and progenitor cells -- Chemically defined -- Wnt signaling -- RNA sequencing -- Transplantation; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121569
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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.