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Flow Cytometry Analysis of Murine Bone Marrow Hematopoietic Stem and Progenitor Cells and Stromal Niche Cells
Published on: September 28, 2022
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Osteoblastic cells regulate the haematopoietic stem cell niche.
L M Calvi1, G B Adams, K W Weibrecht
1Endocrine Unit, Department of Medicine, Center for Human Genetics and Molecular Pediatric Disease, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Nature
|October 24, 2003
Summary
Bone cells regulate blood stem cell numbers via Notch signaling. Parathyroid hormone (PTH) stimulates osteoblasts, increasing hematopoietic stem cells (HSCs) and improving transplant survival.
Area of Science:
- Hematology
- Stem Cell Biology
- Bone Biology
Background:
- Stem cell fate is influenced by microenvironments, but these remain poorly defined in mammals.
- Hematopoiesis, the formation of blood cellular components, is localized within the bone marrow.
Purpose of the Study:
- To investigate if bone-derived regulatory information influences hematopoietic stem cells (HSCs).
- To explore the role of osteoblasts in regulating HSCs within the bone marrow niche.
Main Methods:
- Genetically altered mice with osteoblast-specific, activated PTH/PTHrP receptors (PPRs) were assessed.
- Parathyroid hormone (PTH) was used to activate PPRs in vitro and in vivo.
- Notch activation was assessed, and gamma-secretase inhibition was used to block Notch signaling.
Main Results:
- PPR-stimulated osteoblasts increased in number, producing high levels of Jagged 1, and supported an increase in HSCs with Notch1 activation.
- PTH treatment increased osteoblasts in stromal cultures and augmented ex vivo primitive hematopoietic cell growth, which was blocked by gamma-secretase inhibition.
- PTH injection increased HSCs in wild-type animals and markedly improved survival after bone marrow transplantation.
Conclusions:
- Osteoblastic cells are a regulatory component of the HSC niche, influencing HSC function through Notch activation.
- Targeting niche cells or signaling pathways offers potential therapeutic strategies for stem-cell-based therapies.
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