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 …

YS Tzeng, H Li, YL Kang, WC Chen… - Blood, The Journal …, 2011 - ashpublications.org
YS Tzeng, H Li, YL Kang, WC Chen, WC Cheng, DM Lai
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
The CXC-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 …
Abstract
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.
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