| First Author | Cordeiro Gomes A | Year | 2016 |
| Journal | Immunity | Volume | 45 |
| Issue | 6 | Pages | 1219-1231 |
| PubMed ID | 27913094 | Mgi Jnum | J:259197 |
| Mgi Id | MGI:6142759 | Doi | 10.1016/j.immuni.2016.11.004 |
| Citation | Cordeiro Gomes A, et al. (2016) Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation. Immunity 45(6):1219-1231 |
| abstractText | Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells expressing the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. We show that MPPs resided in HSC niches, where they encountered lineage-instructive differentiation signals. Conditional deletion of the chemokine receptor CXCR4 in MPPs reduced differentiation into common lymphoid progenitors (CLPs), which decreased lymphopoiesis. CXCR4 was required for CLP positioning near Interleukin-7(+) (IL-7) cells and for optimal IL-7 receptor signaling. IL-7(+) cells expressed CXCL12 and the cytokine SCF, were mesenchymal progenitors capable of differentiation into osteoblasts and adipocytes, and comprised a minor subset of sinusoidal endothelial cells. Conditional Il7 deletion in mesenchymal progenitors reduced B-lineage committed CLPs, while conditional Cxcl12 or Scf deletion from IL-7(+) cells reduced HSC and MPP numbers. Thus, HSC maintenance and multilineage differentiation are distinct cell lineage decisions that are both controlled by HSC niches. |
