Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche.

Publication Type:

Journal Article

Authors:

Lo Celso, Cristina; Fleming, Heather E; Wu, Juwell W; Zhao, Cher X; Miake-Lye, Sam; Fujisaki, Joji; Daniel C Côté; Rowe, David W; Lin, Charles P; Scadden, David T

Source:

Nature, Volume 457, Issue 7225, p.92-6 (2009)

Keywords:

Animals, Blood Vessels, Bone Marrow, Cell Division, Cell Separation, Hematopoietic Stem Cells, Mice, Mice, Inbred C57BL, Osteoblasts, Proto-Oncogene Proteins c-kit, Skull, Stem Cell Niche

Abstract:

<p>Stem cells reside in a specialized, regulatory environment termed the niche that dictates how they generate, maintain and repair tissues. We have previously documented that transplanted haematopoietic stem and progenitor cell populations localize to subdomains of bone-marrow microvessels where the chemokine CXCL12 is particularly abundant. Using a combination of high-resolution confocal microscopy and two-photon video imaging of individual haematopoietic cells in the calvarium bone marrow of living mice over time, we examine the relationship of haematopoietic stem and progenitor cells to blood vessels, osteoblasts and endosteal surface as they home and engraft in irradiated and c-Kit-receptor-deficient recipient mice. Osteoblasts were enmeshed in microvessels and relative positioning of stem/progenitor cells within this complex tissue was nonrandom and dynamic. Both cell autonomous and non-autonomous factors influenced primitive cell localization. Different haematopoietic cell subsets localized to distinct locations according to the stage of differentiation. When physiological challenges drove either engraftment or expansion, bone-marrow stem/progenitor cells assumed positions in close proximity to bone and osteoblasts. Our analysis permits observing in real time, at a single cell level, processes that previously have been studied only by their long-term outcome at the organismal level.</p>