Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.
Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.
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DOI：
10.1371/journal.pone.0000641
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发表时间：
2007-07-25
期刊：
影响因子：
3.7
通讯作者：
Avraham HK
中科院分区：
文献类型：
--
作者：
Jiang S;Fu Y;Williams J;Wood J;Pandarinathan L;Avraham S;Makriyannis A;Avraham S;Avraham HK
表征调节干细胞自我更新/分裂和分化的内在和外在因素在决定胚胎干（ES）细胞命运中是至关重要的。胚胎干细胞在体外形成拟胚体（EB）的过程中分化为多种造血谱系，这为阐明控制胚层命运决定和组织形成的分子机制提供了实验平台。大麻素受体1型（CB 1）和大麻素受体2型（CB 2）是G蛋白偶联受体（GPCR）家族的成员，由内源性配体内源性大麻素激活。CB 1受体在脑中表达丰富，而CB 2受体主要在造血细胞中表达。然而，CB 1和CB 2及其同源配体在ES细胞中的表达和确切作用尚不清楚。我们观察到显着的诱导CB 1和CB 2大麻素受体在造血分化的小鼠ES（mES）衍生的胚状体。此外，mES细胞以及ES衍生的胚状体在第7天和第14天表达内源性大麻素，CB 1和CB 2的配体。CB 1和CB 2拮抗剂（分别为AM 251和AM 630）诱导mES细胞死亡，强烈表明内源性大麻素参与mES细胞的存活。用外源性大麻素配体Δ9-THC处理mES细胞导致mES细胞的造血分化增加，而添加AM 251或AM 630则阻断源自mES细胞的胚状体形成。此外，大麻素激动剂诱导的ES-衍生的胚状体，这是特异性抑制CB 1和CB 2拮抗剂的趋化性。这项工作尚未解决以前和大麻素受体，CB 1和CB 2，作为一种新的途径调节小鼠ES细胞分化的组件的功能产生新的信息。这项研究提供了大麻素系统参与ES细胞存活和造血分化的见解。
Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES) cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB) formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation. The cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) are members of the G-protein coupled receptor (GPCR) family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES)-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively) induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Δ9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists. This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights into cannabinoid system involvement in ES cell survival and hematopoietic differentiation.
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影响因子：
3.5
作者：
Huffman, JW;Liddle, J;Martin, BR
通讯作者：
Martin, BR
影响因子：
5.2
作者：
Hart, C;Drewel, D;Hennemann, B
通讯作者：
Hennemann, B
影响因子：
4.3
作者：
Mahmud, N;Patel, H;Hoffman, R
通讯作者：
Hoffman, R
人体免疫组织和白细胞亚群中枢和外周大麻素受体的表达
DOI：
10.1111/j.1432-1033.1995.tb20780.x
发表时间：
1995-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GALIEGUE, S;MARY, S;CASELLAS, P
通讯作者：
CASELLAS, P
影响因子：
20.3
作者：
Kimura, T;Boehmier, AM;Möhie, R
通讯作者：
Möhie, R