TY - JOUR
T1 - Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation
AU - Cordeiro Gomes, Ana
AU - Hara, Takahiro
AU - Lim, Vivian Y.
AU - Herndler-Brandstetter, Dietmar
AU - Nevius, Erin
AU - Sugiyama, Tatsuki
AU - Tani-ichi, Shizue
AU - Schlenner, Susan
AU - Richie, Ellen
AU - Rodewald, Hans Reimer
AU - Flavell, Richard A.
AU - Nagasawa, Takashi
AU - Ikuta, Koichi
AU - Pereira, João Pedro
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/12/20
Y1 - 2016/12/20
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2016.11.004
DO - 10.1016/j.immuni.2016.11.004
M3 - Article
C2 - 27913094
AN - SCOPUS:85006726063
SN - 1074-7613
VL - 45
SP - 1219
EP - 1231
JO - Immunity
JF - Immunity
IS - 6
ER -