Medicine and Health

Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

B. Hadland, B. Varnum-finney, et al.

Discover groundbreaking insights into hematopoietic stem cell formation from hemogenic endothelium through innovative single-cell RNA sequencing. This research, conducted by Brandon Hadland, Barbara Varnum-Finney, and colleagues, unveils critical gene expression dynamics that facilitate HSC development and engrafting capabilities.

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Abstract

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

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