Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells

Aline Roch, Sonja Giger, Mukul Girotra, Vasco Campos, Nicola Vannini, Olaia Naveiras, Samy Gobaa and Matthias P. Lutolf ()
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Aline Roch: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Sonja Giger: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Mukul Girotra: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Vasco Campos: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Nicola Vannini: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Olaia Naveiras: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Samy Gobaa: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Matthias P. Lutolf: Ecole Polytechnique Fédérale de Lausanne (EPFL)

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell–cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00291-3

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DOI: 10.1038/s41467-017-00291-3

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