FBS Colloquia No.346Laboratory of Stem Cell Biology and Developmental Immunology

CAR cell-derived CXCL12 maintains lymphoid-biased HSCs with specificity

Hematopoietic stem cells (HSCs) give rise to most blood cells throughout life, and are primarily maintained by adhering to CAR cells, which are bone marrow-specific fibroblasts. CAR cells express high levels of cytokines CXCL12 and SCF, which are essential for HSC maintenance. However, it was reported that the number of HSCs did not decrease when CXCL12 was deleted in about 70% of CAR cells. Thus, we generated mice in which CXCL12 can be deleted in part or all of CAR cells, and mice in which CXCL12-deficient CAR cells can be visualized separately from CXCL12-intact CAR cells and clarified the roles of CAR cell-derived CXCL12 in HSCs and hematopoiesis, and their mechanisms. (Nakatani T. et al., Nat. Commun. 2023)