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

• Published in: Blood Vol. 117; no. 2; pp. 429 - 439
• Main Authors: Tzeng, Yi-Shiuan, Li, Hung, Kang, Yuan-Lin, Chen, Wen-Cheng, Cheng, Wei-Cheng, Lai, Dar-Ming
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 13.01.2011; Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Chemokine CXCL12 - deficiency; Chemokine CXCL12 - metabolism; Flow Cytometry; Fluorescent Antibody Technique; Granulocyte Precursor Cells - cytology; Granulocyte Precursor Cells - metabolism; Hematologic and hematopoietic diseases; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Regeneration; Reverse Transcriptase Polymerase Chain Reaction; Stem Cell Niche; Stromal cell derived factor 1; Regeneration; Hematology; Stem cell; Adult animal; Hematopoietic cell; Myelosuppression
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-01-266833

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.