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Live-animal imaging of native hematopoietic stem and progenitor cells
- Source :
- Nature
- Publication Year :
- 2020
-
Abstract
- The biology of hematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions1,2. Particularly challenging has been the study of dynamic HSC behaviors given that live animal HSC visualization in the native niche still represents an elusive goal in the field. Here, we describe a dual genetic strategy in mice that restricts reporter labeling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow (BM)3–5. We find that this subset of LT-HSCs resides in close proximity to both sinusoidal blood vessels and the endosteal surface. In contrast, multipotent progenitor cells (MPPs) display a broader distance distribution from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in BM niches with the deepest hypoxia and instead are found in similar hypoxic environments as MPPs. In vivo time-lapse imaging reveals that LT-HSCs display limited motility at steady-state. Following activation, LT-HSCs display heterogenous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of BM cavities exhibiting bone-remodeling activities. In contrast, cavities with low bone-resorbing activities do not harbor expanding HSCs. These findings point to a new degree of heterogeneity within the BM microenvironment, imposed by the stages of bone turnover. Overall, our approach enables direct visualization of HSC behaviors and dissection of heterogeneity in HSC niches.
- Subjects :
- 0301 basic medicine
Endosteum
Multidisciplinary
Motility
hemic and immune systems
single-cell sequencing
Biology
Article
Bone remodeling
Cell biology
Transplantation
03 medical and health sciences
Haematopoiesis
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
030220 oncology & carcinogenesis
medicine
Bone marrow
Stem cell
Progenitor cell
Subjects
Details
- Language :
- English
- ISSN :
- 14764687 and 00280836
- Volume :
- 578
- Issue :
- 7794
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....08a4eedb6ab64fc6eed1e10bd3e42e40