Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation
| Autor: | Vivian Y. Lim, Koichi Ikuta, João Pereira, Dietmar Herndler-Brandstetter, Erin Nevius, Ellen R. Richie, Richard A. Flavell, Hans Reimer Rodewald, Tatsuki Sugiyama, Takashi Nagasawa, Shizue Tani-ichi, Takahiro Hara, Ana Cordeiro Gomes, Susan M. Schlenner |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine CXCL2 Immunology Mice Transgenic Cell Separation Biology Mice 03 medical and health sciences Chemokine receptor medicine Animals Immunology and Allergy Cell Lineage Lymphopoiesis Stem Cell Niche Progenitor cell Interleukin-7 Multipotent Stem Cells Mesenchymal stem cell Hematopoietic stem cell Cell Differentiation Flow Cytometry Hematopoietic Stem Cells Cell biology Mice Inbred C57BL Haematopoiesis 030104 developmental biology Infectious Diseases medicine.anatomical_structure Bone marrow Stem cell |
| Zdroj: | Immunity. 45:1219-1231 |
| ISSN: | 1074-7613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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