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Combining Intravital Fluorescent Microscopy (IVFM) with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
Published on: March 21, 2017
Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency.
Alexandra Berger1, Catherine Frelin, Divya K Shah
1Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
Plos One
|March 22, 2013
Summary
Neurokinin-1 receptor (NK-1R) signaling is crucial for adult hematopoiesis, as NK-1R deficient stem cells show impaired B and T cell engraftment. Tachykinin peptides SP and HK-1 do not appear essential for this process in vivo.
Area of Science:
- Neuroscience
- Hematology
- Stem Cell Biology
Background:
- Tachykinins are neuropeptides with known central and peripheral roles.
- In vitro studies suggest tachykinins support stem cell growth, but in vivo relevance is unclear.
- Neurokinin-1 receptor (NK-1R) mediates tachykinin actions.
Purpose of the Study:
- To investigate the in vivo role of NK-1R signaling in adult hematopoietic stem cell function.
- To determine if tachykinin peptides are essential for hematopoietic stem cell repopulation in vivo.
Main Methods:
- Competitive bone marrow repopulation assays were performed using hematopoietic stem cells from NK-1R deficient mice (Tacr1(-/-)).
- Hematopoietic stem cell function was assessed by analyzing B and T cell engraftment.
- Tachykinin peptide knockout mice (Tac1(-/-), Tac4(-/-), and Tac1(-/-)/Tac4(-/-)) were used to study peptide-specific roles.
Main Results:
- NK-1R deficient bone marrow exhibited lineage-specific deficits in B and T cell engraftment compared to wild-type cells.
- Mice lacking tachykinin peptides SP and/or HK-1 showed normal hematopoietic stem cell repopulation efficiency.
- These findings suggest a host-derived, rather than stem cell-intrinsic, role for tachykinins in hematopoiesis.
Conclusions:
- NK-1R signaling is essential for normal adult hematopoiesis, specifically for B and T cell development.
- The mechanism of action appears to be paracrine or endocrine, with tachykinin peptides supplied by the host environment.
- Tachykinin peptides themselves (SP, HK-1) are not required for hematopoietic stem cell function in vivo.
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