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

Yun Chang, Ramizah Syahirah, Stephanie N. Oprescu, Xuepeng Wang, Juhyung Jung, Scott H. Cooper, Sandra Torregrosa-Allen, Bennett D. Elzey, Alan Y. Hsu, Lauren N. Randolph, Yufei Sun, Shihuan Kuang, Hal E. Broxmeyer, Qing Deng, Xiaojun Lian, Xiaoping Bao

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Article number121569
JournalBiomaterials
Volume285
DOIs
StatePublished - Jun 2022

All Science Journal Classification (ASJC) codes

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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