Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression.
The C-X-C-type chemokine Cxcl12, also known as stromal cell-derived factor-1, plays a critical role in hematopoiesis during fetal development. However, the functional requirement of Cxcl12 in the adult hematopoietic stem/progenitor cell (HSPC) regulation was still unclear. In this report, we developed a murine Cxcl12 conditional deletion model in which the target gene can be deleted at the adult stage. We found that loss of stroma-secreted Cxcl12 in the adult led to expansion of the HSPC population as well as a reduction in long-term quiescent stem cells. In Cxcl12-deficient bone marrow, HSPCs were absent along the endosteal surface, and blood cell regeneration occurred predominantly in the perisinusoidal space after 5-fluorouracil myelosuppression challenge. Our results indicate that Cxcl12 is required for HSPC homeostasis regulation and is an important factor for osteoblastic niche organization in adult stage bone marrow.
Tzeng
Yi-Shiuan
YS
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Li
Hung
H
Kang
Yuan-Lin
YL
Chen
Wen-Cheng
WC
Cheng
Wei-Cheng
WC
Lai
Dar-Ming
DM
D000818:Animals; D054377:Chemokine CXCL12 / Q000172:deficiency / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D042381:Granulocyte Precursor Cells / Q000166:cytology / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055153:Stem Cell Niche
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse