Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation.
Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation.
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DOI：
10.1016/j.immuni.2016.11.004
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发表时间：
2016-12-20
期刊：
影响因子：
32.4
通讯作者：
Pereira JP
中科院分区：
文献类型：
--
作者：
Cordeiro Gomes A;Hara T;Lim VY;Herndler-Brandstetter D;Nevius E;Sugiyama T;Tani-Ichi S;Schlenner S;Richie E;Rodewald HR;Flavell RA;Nagasawa T;Ikuta K;Pereira JP
造血干细胞（HSC）在表达趋化因子CXCL 12的间充质祖细胞和内皮细胞形成的骨髓小生境中自我更新，但是否有一个单独的小生境指导多能祖细胞（MPP）分化仍不清楚。在这里，我们表明，MPPs居住在HSC壁龛，他们遇到了谱系指导分化信号。MPP中趋化因子受体CXCR 4的条件性缺失减少了向普通淋巴祖细胞（CLP）的分化，从而减少了淋巴细胞生成。CXCR 4是CLP定位在白细胞介素-7+（IL-7）细胞附近以及最佳IL-7受体信号传导所需的。IL-7+细胞表达CXCL 12和SCF，是能够分化为成骨细胞和脂肪细胞的间充质祖细胞，并且包括窦内皮细胞的小子集。间充质祖细胞中的条件性Il 7缺失减少了B系定向CLP，而IL-7+细胞中的条件性Cxcl 12或Scf缺失减少了HSC和MPP的数量。因此，HSC维持和多谱系分化是不同的细胞谱系决定，都是由HSC小生境控制的。
Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells that express the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. Here, 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 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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DOI：
10.1084/jem.20042393
发表时间：
2005-03-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dias S;Silva H Jr;Cumano A;Vieira P
通讯作者：
Vieira P
影响因子：
64.5
作者：
McDermott, David H.;Gao, Ji-Liang;Murphy, Philip M.
通讯作者：
Murphy, Philip M.
影响因子：
10.5
作者：
Inlay, Matthew A.;Bhattacharya, Deepta;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
DOI：
10.1073/pnas.95.16.9448
发表时间：
1998-08-04
影响因子：
11.1
作者：
Ma, Q;Jones, D;Springer, TA
通讯作者：
Springer, TA
影响因子：
4.4
作者：
Hara, Takahiro;Shitara, Soichiro;Ikuta, Koichi
通讯作者：
Ikuta, Koichi