PUBLICATION

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

Authors
Chang, Y., Syahirah, R., Oprescu, S.N., Wang, X., Jung, J., Cooper, S.H., Torregrosa-Allen, S., Elzey, B.D., Hsu, A.Y., Randolph, L.N., Sun, Y., Kuang, S., Broxmeyer, H.E., Deng, Q., Lian, X., Bao, X.
ID
ZDB-PUB-220515-26
Date
2022
Source
Biomaterials   285: 121569 (Journal)
Registered Authors
Deng, Qing, Hsu, Alan, Syahirah Mohd Sabri, Ramizah
Keywords
Chemically defined, Hematopoietic stem and progenitor cells, RNA sequencing, Stem cell differentiation, Transplantation, Wnt signaling
MeSH Terms
  • Animals
  • Cell Differentiation/physiology
  • Hemangioblasts*
  • Hematopoiesis/physiology
  • Hematopoietic Stem Cells
  • Humans
  • Mesonephros
  • Mice
  • Zebrafish
PubMed
35567999 Full text @ Biomaterials
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping