Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation

被引：224

作者：

Gomes, Ana Cordeiro ^{[1
,2
]}

Hara, Takahiro ^{[3
]}

Lim, Vivian Y. ^{[1
]}

Herndler-Brandstetter, Dietmar ^{[1
]}

Nevius, Erin ^{[1
]}

Sugiyama, Tatsuki ^{[4
,5
,6
]}

Tani-ichi, Shizue ^{[3
]}

Schlenner, Susan ^{[7
,8
]}

Richie, Ellen ^{[10
]}

Rodewald, Hans-Reimer ^{[9
]}

Flavell, Richard A. ^{[1
,11
]}

Nagasawa, Takashi ^{[4
,5
,6
]}

Ikuta, Koichi ^{[3
]}

Pereira, Joao Pedro ^{[1
]}

机构：

[1] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

[2] Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099002 Oporto, Portugal

[3] Kyoto Univ, Inst Virus Res, Dept Biol Responses, Lab Biol Protect, Kyoto 6068507, Japan

[4] Kyoto Univ, Inst Frontier Med Sci, Dept Immunobiol & Hematol, Kyoto 6068507, Japan

[5] Osaka Univ, Grad Sch Frontier Biosci, Lab Stem Cell Biol & Dev Immunol, 1-3 Yamada Oka, Suita, Osaka 5650871, Japan

[6] Osaka Univ, Grad Sch Med, 1-3 Yamada Oka, Suita, Osaka 5650871, Japan

[7] VIB, Autoimmune Genet Lab, B-3000 Leuven, Belgium

[8] Univ Leuven, Dept Microbiol & Immunol, B-3000 Leuven, Belgium

[9] German Canc Res Ctr, Div Cellular Immunol, D-69120 Heidelberg, Germany

[10] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Dept Mol Carcinogenesis, Smithville, TX 78957 USA

[11] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

IMMUNITY | 2016年 / 45卷 / 06期

基金：

奥地利科学基金会;

关键词：

EARLY LYMPHOID PROGENITORS; CHEMOKINE RECEPTOR CXCR4; BONE-MARROW NICHE; B-LYMPHOPOIESIS; STEM/PROGENITOR CELLS; CRE RECOMBINASE; ADULT MICE; MAINTENANCE; EXPRESSION; MAINTAIN;

D O I：

10.1016/j.immuni.2016.11.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：1219 / 1231

页数：13

共 52 条

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