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

By Cristina Lo Celso, H. Fleming, Juwell W. Wu, Cher X. Zhao, Sam Miake-Lye, Joji Fujisaki, D. Côté, D. Rowe, Charles P. Lin, D. Scadden. Nature, 2008

934 citations recorded by the source corpus.

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.

Subfields: Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/814a8bedda710e9a12a4c65cec51b1c2b8efe72b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hematology

1. G. Semenza
2. T. Suda
3. P. Frenette
4. K. Takubo
5. D. Scadden
6. S. Morrison

In Immunology

1. Miriam Merad
2. H. Kronenberg
3. D. Hashimoto
4. D. Scadden
5. G. Semenza
6. P. Frenette

Citations in the corpus

• Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants in Bone Maintenance and Regeneration (2012, methodology): “…Vivo Imaging To image YFP+ osteoblasts and osteogenic progenitors in vivo, indicated mice were anesthetized and prepared for a custom-built two-photon and confocal hybrid microscope specifically designed for live animal imaging as described previously (Sipkins et al., 2005) (Lo Celso et al., 2009).”
• Extracellular matrix: A dynamic microenvironment for stem cell niche (2014, background): “In fact, sophisticated three-dimensional imaging allowed revealing that there are intimate contacts between these two types of niche elements [121,122] and that HSCs canmove among these niches quite readily and receive inputs from both of them simultaneously [123].”
• Metabolic regulation of hematopoietic stem cells in the hypoxic niche. (2011, background): “Real-time imaging of murine BM in calvaria revealed that HSCs gradually move away from vessels and then dive deep into the osteoblastic region of the BM after transplantation (Lo Celso et al., 2009; Xie et al., 2009).”
• Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche (2011, background): “HSCs are retained in perivascular niches that are distributed near osteoblasts and within the nonendosteal parenchyma (Kiel et al., 2005; Sugiyama et al., 2006; Lo Celso et al., 2009; Méndez-Ferrer et al., 2010b).”