SDF1CXCL12

SDF1CXCL12 is a chemokine also known as stromal cell-derived factor 1 (SDF-1) and is encoded by the CXCL12 gene. In humans, CXCL12 resides on chromosome 10q11.21 and undergoes alternative splicing to produce several isoforms, including CXCL12a (SDF-1α) and CXCL12β (SDF-1β). These isoforms share the core CXC chemokine domain but vary in their C-terminal sequences, affecting stability and localization.

The secreted CXCL12 protein functions as a chemoattractant that guides the migration of various cell types, notably hematopoietic stem and progenitor cells, endothelial cells, and neural crest–derived cells. Its biological effects are largely mediated through the CXCR4 receptor, a G protein–coupled receptor, while ACKR3 (CXCR7) can also bind CXCL12 and shape signaling. CXCL12–CXCR4 signaling activates Gi/o proteins, leading to changes in cAMP, intracellular calcium, and downstream pathways such as PI3K–Akt and MAPK–ERK, promoting chemotaxis, survival, and adhesion.

Regulation and roles: CXCL12 is produced by stromal cells in the bone marrow and by various tissues, with expression enhanced by hypoxia via HIF-1. The CXCL12 gradient contributes to stem cell homing to and retention within the bone marrow and participates in angiogenesis, cardiovascular and nervous system development, and immune cell trafficking. In disease, the CXCL12–CXCR4 axis can facilitate cancer metastasis to CXCL12-rich organs and modulate inflammatory responses and tissue repair.

Clinical relevance: pharmacological disruption of CXCL12–CXCR4 signaling, for example with the antagonist plerixafor (AMD3100), is used to mobilize hematopoietic stem cells for transplantation. The axis is also explored as a therapeutic target in cancer and regenerative medicine, and CXCL12–CXCR4 interactions influence HIV entry via CXCR4.