FBS Colloquia No.403Laboratory of Stem Cell Biology and Developmental Immunology

Universal fibroblasts across tissues can differentiate into niche cells for hematopoietic stem cells

Hematopoietic stem cells (HSCs) generating all blood cells are maintained by their niche cells, termed CXCL12-abundant reticular (CAR) cells in the bone marrow. A meta-analysis of single-cell RNA sequencing datasets across tissues hypothesized that universal fibroblasts present in all organs give rise to distinct tissue-specific fibroblast subsets designated as specialized fibroblasts, including CAR cells. However, there is no direct evidence that universal fibroblasts can differentiate into specialized fibroblasts at distant location. Here we demonstrated that CD248+ universal fibroblasts from the lung and colon outside the skeletal system as well as muscle generated CAR cells characterized by HSC niche functions and expression of cytokines and transcription factors essential for HSC maintenance during ectopic bone formation or after intra-bone marrow transplantation. These results demonstrate that universal fibroblasts with the potential to differentiate into bone marrow-specific HSC niche cells are scattered throughout the entire body.