Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment

Kim Vanuytsel (), Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Zhe Wang, Wilfredo F. Garcia-Beltran, Vladimir Vrbanac, Dylan Parsons, Evan C. Lam, Taylor M. Matte, Todd W. Dowrey, Sara S. Kumar, Mengze Li, Feiya Wang, Anthony K. Yeung, Gustavo Mostoslavsky, Ruben Dries, Joshua D. Campbell, Anna C. Belkina, Alejandro B. Balazs () and George J. Murphy ()
Additional contact information
Kim Vanuytsel: Boston University
Carlos Villacorta-Martin: Boston University and Boston Medical Center
Jonathan Lindstrom-Vautrin: Boston University and Boston Medical Center
Zhe Wang: Boston University
Wilfredo F. Garcia-Beltran: Ragon Institute of MGH, MIT and Harvard
Vladimir Vrbanac: Ragon Institute of MGH, MIT and Harvard
Dylan Parsons: Ragon Institute of MGH, MIT and Harvard
Evan C. Lam: Ragon Institute of MGH, MIT and Harvard
Taylor M. Matte: Boston University and Boston Medical Center
Todd W. Dowrey: Boston University and Boston Medical Center
Sara S. Kumar: Boston University and Boston Medical Center
Mengze Li: Boston University
Feiya Wang: Boston University and Boston Medical Center
Anthony K. Yeung: Boston University and Boston Medical Center
Gustavo Mostoslavsky: Boston University and Boston Medical Center
Ruben Dries: Boston University
Joshua D. Campbell: Boston University
Anna C. Belkina: Boston University
Alejandro B. Balazs: Ragon Institute of MGH, MIT and Harvard
George J. Murphy: Boston University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, hematopoietic stem cells in the fetal liver undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. Here, we profile 26,407 fetal liver cells at both the transcriptional and protein level including ~7,000 highly enriched and functional fetal liver hematopoietic stem cells to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression reveals a generalizable signature defining functional fetal liver hematopoietic stem cells and allows for the stratification of enrichment strategies with high translational potential. More precisely, our integrated analysis identifies CD201 (endothelial protein C receptor (EPCR), encoded by PROCR) as a marker that can specifically enrich for engraftment potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers. As such, it serves as a useful resource for the field and forms the basis for further biological exploration of strategies to retain the engraftment potential of hematopoietic stem cells ex vivo or induce this potential during in vitro hematopoietic stem cell generation.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28616-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28616-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28616-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().