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

• Published in: Nature (London) Vol. 457; no. 7225; pp. 92 - 96
• Main Authors: Lin, Charles P, Scadden, David T, Celso, Cristina Lo, Fleming, Heather E, Wu, Juwell W, Zhao, Cher X, Miake-Lye, Sam, Fujisaki, Joji, Côté, Daniel, Rowe, David W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2009; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Blood Vessels - cytology; Bone Marrow; Cell differentiation, maturation, development, hematopoiesis; Cell Division; Cell physiology; Cell Separation; Confocal microscopy; Drug therapy; Fundamental and applied biological sciences. Psychology; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Humanities and Social Sciences; letter; Mice; Mice, Inbred C57BL; Microscopy; Molecular and cellular biology; multidisciplinary; Osteoblasts; Osteoblasts - cytology; Physiological aspects; Postoperative period; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Science; Science (multidisciplinary); Skull - cytology; Stem Cell Niche - cytology; Stem cells; United States; Stem cell; Rodentia; Hematopoietic cell; Confocal microscopy; Real time; Osteoarticular system; Microcirculation; Vertebrata; Calvaria; Mammalia; Mouse; Bone marrow; Osteoblast; Bone; Progenitor cell
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature07434

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.