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

Author

Listed:
  • Kim Vanuytsel

    (Boston University
    Boston University and Boston Medical Center)

  • 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
    Boston University)

  • Joshua D. Campbell

    (Boston University)

  • Anna C. Belkina

    (Boston University
    Boston University)

  • Alejandro B. Balazs

    (Ragon Institute of MGH, MIT and Harvard)

  • George J. Murphy

    (Boston University
    Boston University and Boston Medical Center)

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.

Suggested Citation

  • 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, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28616-x
    DOI: 10.1038/s41467-022-28616-x
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