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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
ERK1 regulates the hematopoietic stem cell niches
Nathalie Saulnier1, Soizic Guihard, Xavier Holy
1Institut Cochin, Université Paris Descartes, Sorbonne Paris Descartes, CNRS (UMR 8104), Paris, France.
Plos One
|February 4, 2012
Summary
The study reveals that ERK1 is crucial for maintaining the bone marrow microenvironment and proper hematopoietic stem cell (HSC) homing. ERK1 deficiency impairs osteoclastogenesis and mononuclear-phagocyte development by affecting M-CSF receptor expression.
Area of Science:
- Cell Biology
- Hematology
- Immunology
Background:
- Mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are key signal transducers with incompletely understood in vivo functions.
- Limited in vivo studies exist on ERK1/ERK2 roles in hematopoietic stem cells (HSCs) and the bone marrow microenvironment.
Purpose of the Study:
- To investigate the in vivo function of ERK1 in HSCs and the bone marrow microenvironment.
- To elucidate the role of ERK1 in osteoclastogenesis and myeloid progenitor development.
Main Methods:
- Utilized ERK1-deficient mice and performed serial transplantations.
- Assessed HSC lodging, homing, and engraftment capabilities.
- Analyzed osteoclastogenesis, osteoblast activity, and myeloid progenitor populations (CMPs, GMPs).
- Investigated M-CSF receptor expression on myeloid progenitors.
Main Results:
- ERK1-deficient mice exhibited mild osteopetrosis, impaired HSC lodging/homing, and defective medullar microenvironment maintenance.
- ERK1 deletion compromised osteoclastogenesis but not osteoblast activity.
- Myeloid progenitor analysis showed increased common myeloid progenitors (CMPs) and decreased granulocyte-macrophage progenitors (GMPs).
- Reduced M-CSF receptor expression on myeloid progenitors impaired mononuclear-phagocyte lineage development.
Conclusions:
- ERK1 is essential for maintaining the bone marrow microenvironment and proper HSC engraftment.
- ERK1 regulates osteoclastogenesis and myeloid progenitor development via M-CSF receptor signaling.
- This study highlights an ERK1-dependent regulation of M-CSF receptor on hematopoietic progenitors, suggesting cross-talk between HSCs, progeny, and bone cells.
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