To identify signals responsible for hematopoietic stem cell (HSC) formation from hemogenic endothelium (HE), single-cell RNA sequencing analyzed AGM-derived cells transitioning from HE to HSCs and niche endothelial cells. Pseudotemporal ordering revealed gene expression dynamics, identifying developing HSC surface receptors and corresponding niche cell ligands. An engineered platform integrating these ligands (Notch, VLA-4 integrin, CXCR4) supported engrafting HSC generation, providing a transcriptional map of HSC development signaling interactions for therapeutic applications.
Publisher
Nature Communications
Published On
Mar 24, 2022
Authors
Brandon Hadland, Barbara Varnum-Finney, Stacey Dozono, Tessa Dignum, Cynthia Nourigat-McKay, Adam M. Heck, Takashi Ishida, Dana L. Jackson, Tomer Itkin, Jason M. Butler, Shahin Rafii, Cole Trapnell, Irwin D. Bernstein
Tags
hematopoietic stem cells
hemogenic endothelium
single-cell RNA sequencing
gene expression dynamics
therapeutic applications
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