Abstract
Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hematopoietic compartment, including hematopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2-/- HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although α4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hematopoietic defect in Dock2-/- mice. Long-term engraftment of transplanted Dock2-/- BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2-/- lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal.
| Original language | English |
|---|---|
| Pages (from-to) | 90-96 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 367 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Feb 29 2008 |
Fingerprint
Keywords
- CXCL12
- CXCR4
- Dock2
- Hematopoietic stem/progenitor cells
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Dock2 participates in bone marrow lympho-hematopoiesis. / Kikuchi, Tomoko; Kubonishi, Shiro; Shibakura, Misako; Namba, Noriko; Matsui, Toshimitsu; Fukui, Yoshinori; Tanimoto, Mitsune; Katayama, Yoshio.
In: Biochemical and Biophysical Research Communications, Vol. 367, No. 1, 29.02.2008, p. 90-96.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dock2 participates in bone marrow lympho-hematopoiesis
AU - Kikuchi, Tomoko
AU - Kubonishi, Shiro
AU - Shibakura, Misako
AU - Namba, Noriko
AU - Matsui, Toshimitsu
AU - Fukui, Yoshinori
AU - Tanimoto, Mitsune
AU - Katayama, Yoshio
PY - 2008/2/29
Y1 - 2008/2/29
N2 - Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hematopoietic compartment, including hematopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2-/- HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although α4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hematopoietic defect in Dock2-/- mice. Long-term engraftment of transplanted Dock2-/- BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2-/- lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal.
AB - Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hematopoietic compartment, including hematopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2-/- HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although α4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hematopoietic defect in Dock2-/- mice. Long-term engraftment of transplanted Dock2-/- BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2-/- lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal.
KW - CXCL12
KW - CXCR4
KW - Dock2
KW - Hematopoietic stem/progenitor cells
UR - http://www.scopus.com/inward/record.url?scp=38049129792&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38049129792&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.12.093
DO - 10.1016/j.bbrc.2007.12.093
M3 - Article
C2 - 18157938
AN - SCOPUS:38049129792
VL - 367
SP - 90
EP - 96
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -