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

Abstract

Stem cells reside in a specialized, regulatory environment termed the niche that dictates how they generate, maintain and repair tissues1,2. 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 abundant3. 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.

Adipocytic Cells Augment the Support of Primitive Hematopoietic Cells In Vitro But Have No Effect in the Bone Marrow Niche Under Homeostatic Conditions

“…However, to formally rule out adipocytes as being active in the hematopoietic niche under homesostatic conditions, direct visualization of the HSCs in real time would have to be performed. Unfortunately, this has only been achieved with moderate success recently [41,42]. Our functional data thus argue against a role of adipocytes in the HSC niche under homeostatic conditions.…”

Optical Barcoding for Single-Clone Tracking to Study Tumor Heterogeneity

“…In an increasing number of research areas, including investigations of cancer stem cells, tissue renewal, 19,20 neurogenesis, 21 network formation, 7 and hematopoiesis or immunology, 22 www.moleculartherapy.org complex systems in health and disease. In order to distinguish the unique properties of such subpopulations, the heterogeneous biological systems and the interplay between the individual components need to be analyzed at the cellular level.…”

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

“…These results suggest that PTH affects the distribution of these early precursors, possibly by altering their niche. (20,25,32,33) These alterations could be due to a direct effect of PTH on the cells supporting the stability of hematopoietic niches or, alternatively, as a product of increased osteoclasto- genesis. This latter possibility has been documented in recent years in studies showing that osteoclast activity may play a role in the dynamics of the hematopoietic niche.…”