CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance.
CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance.
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造血干细胞（hsc）主要存在于骨髓中，由骨髓基质细胞产生的信号调节其自我更新、增殖和运输。内皮成骨细胞和血管周围基质细胞，包括内皮细胞、富含cxcl12的网状细胞、瘦素受体阳性基质细胞和巢蛋白绿色荧光蛋白（GFP）阳性间充质祖细胞，都与HSC的维持有关。然而，目前尚不清楚特定的造血祖细胞（HPC）亚群是否存在于由周围基质细胞及其产生的调节分子所定义的不同生态位中。CXCL12（趋化因子（C-X-C基序）配体12）调节造血干细胞和淋巴样祖细胞，并在所有这些基质细胞群中表达，，，，。在这里，我们选择性地从候选小生境基质细胞群中删除了cxcl12，并表征了其对HPCs的影响。从矿化成骨细胞中删除cxcl12对造血干细胞或淋巴样祖细胞没有影响。从表达骨的基质细胞（包括富含cxcl12的网状细胞和成骨细胞）中删除cxcl12，会导致构成性HPC动员和b淋巴样祖细胞的丢失，但HSC功能正常。内皮细胞中的cxcl12缺失导致长期再生活性的适度丧失。引人注目的是，从使用prx1 - cre（prx1也称为asPrrx1）的巢蛋白阴性间充质祖细胞中删除cxcl12与HSC的显著缺失、长期再生活性、HSC静止和常见淋巴样祖细胞相关。这些数据表明，表达osterix的基质细胞包含一个独特的生态位，支持b淋巴样祖细胞并保留骨髓中的HPCs，并且来自血管周围区域的基质细胞（包括内皮细胞和间充质祖细胞）的CXCL12表达支持造血干细胞。
Haematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation and trafficking. Endosteal osteoblasts,and perivascular stromal cells including endothelial cells, CXCL12-abundant reticular cells,, leptin-receptor-positive stromal cells, and nestin–green fluorescent protein (GFP)-positive mesenchymal progenitors have all been implicated in HSC maintenance. However, it is unclear whether specific haematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (chemokine (C–X–C motif) ligand 12) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations,,,,. Here we selectively deletedCxcl12from candidate niche stromal cell populations and characterized the effect on HPCs. Deletion ofCxcl12from mineralizing osteoblasts has no effect on HSCs or lymphoid progenitors. Deletion ofCxcl12from osterix-expressing stromal cells, which include CXCL12-abundant reticular cells and osteoblasts, results in constitutive HPC mobilization and a loss of B-lymphoid progenitors, but HSC function is normal.Cxcl12deletion from endothelial cells results in a modest loss of long-term repopulating activity. Strikingly, deletion of Cxcl12from nestin-negative mesenchymal progenitors usingPrx1–cre(Prx1also known asPrrx1) is associated with a marked loss of HSCs, long-term repopulating activity, HSC quiescence and common lymphoid progenitors. These data suggest that osterix-expressing stromal cells comprise a distinct niche that supports B-lymphoid progenitors and retains HPCs in the bone marrow, and that expression of CXCL12 from stromal cells in the perivascular region, including endothelial cells and mesenchymal progenitors, supports HSCs.
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小鼠骨髓中多能间充质干细胞的前瞻性鉴定、分离和系统移植。
DOI：
10.1084/jem.20091046
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Morikawa S;Mabuchi Y;Kubota Y;Nagai Y;Niibe K;Hiratsu E;Suzuki S;Miyauchi-Hara C;Nagoshi N;Sunabori T;Shimmura S;Miyawaki A;Nakagawa T;Suda T;Okano H;Matsuzaki Y
通讯作者：
Matsuzaki Y
影响因子：
64.5
作者：
Sacchetti, Benedetto;Funari, Alessia;Bianco, Paolo
通讯作者：
Bianco, Paolo
影响因子：
32.4
作者：
Omatsu, Yoshiki;Sugiyama, Tatsuki;Nagasawa, Takashi
通讯作者：
Nagasawa, Takashi
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
15.3
作者：
Nie, Yuchun;Han, Yoon-Chi;Zou, Yong-Rui
通讯作者：
Zou, Yong-Rui