Intravital Imaging Reveals Motility of Adult Hematopoietic Stem Cells in the Bone Marrow Niche

Samik Upadhaya, Oleg Krichevsky, Ilseyar Akhmetzyanova, Catherine M. Sawai, David R. Fooksman, Boris Reizis

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Adult mammalian hematopoietic stem cells (HSCs) reside in the bone marrow (BM) but can be mobilized into blood for use in transplantation. HSCs interact with BM niche cells that produce growth factor c-Kit ligand (Kitl/SCF) and chemokine CXCL12, and were thought to be static and sessile. We used two-photon laser scanning microscopy to visualize genetically labeled HSCs in the BM of live mice for several hours. The majority of HSCs showed a dynamic non-spherical morphology and significant motility, undergoing slow processive motion interrupted by short stretches of confined motion. HSCs moved in the perivascular space and showed intermittent close contacts with SCF-expressing perivascular stromal cells. In contrast, mobilization-inducing blockade of CXCL12 receptor CXCR4 and integrins rapidly abrogated HSC motility and shape dynamics in real time. Our results reveal an unexpectedly dynamic nature of HSC residence in the BM and interaction with the SCF+ stromal niche, which is disrupted during HSC mobilization.

Original languageEnglish (US)
Pages (from-to)336-345.e4
JournalCell Stem Cell
Volume27
Issue number2
DOIs
StatePublished - Aug 6 2020

Keywords

  • CXCR4
  • bone marrow
  • hematopoietic stem cells
  • integrins
  • intravital microscopy
  • mobilization
  • motility
  • stem cell niche
  • stronal cells

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Cell Biology

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