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Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis
Published on: May 26, 2021
Dock2 participates in bone marrow lympho-hematopoiesis
Tomoko Kikuchi1, Shiro Kubonishi, Misako Shibakura
1Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Biochemical and Biophysical Research Communications
|December 26, 2007
Summary
Dock2 is crucial for the development of lymphocytes in bone marrow, but it is not essential for hematopoietic stem cell engraftment or self-renewal. This study clarifies Dock2
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Dock2 is known to be essential for mature lymphocyte chemotaxis.
- The role of Dock2 in immature hematopoietic cells remains largely unknown.
Purpose of the Study:
- To investigate the expression and function of Dock2 in immature hematopoietic cells.
- To determine the role of Dock2 in hematopoietic stem cell (HSC) function and bone marrow (BM) lymphopoiesis.
Main Methods:
- Expression analysis of Dock2 in BM hematopoietic compartments.
- Chemotaxis and actin polymerization assays of Dock2-deficient (Dock2-/-) hematopoietic progenitor cells (HPCs) in response to CXCL12.
- In vivo studies using 5-FU administration and bone marrow transplantation in Dock2-/- mice.
Main Results:
- Dock2 is broadly expressed in the BM hematopoietic compartment, including HSC/HPC fractions.
- Dock2-/- HPCs showed impaired chemotaxis and actin polymerization in response to CXCL12.
- Dock2 deficiency did not cause hematopoietic defects in vivo under myelosuppressive stress.
- Long-term engraftment of Dock2-/- BM cells was impaired due to defective lymphoid precursor competition, not intrinsic HSC defects.
Conclusions:
- Dock2 plays a significant role in bone marrow lymphopoiesis.
- Dock2 is dispensable for hematopoietic stem cell engraftment and self-renewal.
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