Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, IUIN, CIBERNED and IRYCIS, 28040 Madrid, Spain.
Prog Lipid Res. 2013 Oct;52(4):633-50. doi: 10.1016/j.plipres.2013.05.004. Epub 2013 Sep 25.
Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS). The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes. Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved. Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm). In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation. Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells. Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery. The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.
大麻素是大麻（Cannabis sativa）提取物中的活性成分，几个世纪以来一直引起人类的关注，其出现时间远早于其作用底物内源性大麻素系统（endocannabinoid system，ECS）的发现和特征描述。ECS 是由内源性脂质、其受体（特别是 1 型（CB1）和 2 型（CB2）大麻素受体）和代谢酶组成的集合体。大麻素信号调节细胞增殖、分化和存活，其结果因涉及的分子靶标和细胞环境而异。大麻素受体从早期发育阶段就有表达和功能，此时它们调节胚胎和滋养层干细胞的存活和分化，因此可能会影响来自三个不同胚层（外胚层、中胚层和内胚层）的多种成年特化组织的形成。在外胚层衍生的神经系统中，CB1 和 CB2 受体均存在于神经祖细胞/干细胞中，并控制其自我更新、增殖和分化。CB1 和 CB2 的表达模式相反，前者在神经元分化过程中增加，后者减少。最近，内源性大麻素（endocannabinoid，eCB）信号也被证明可以调节中胚层衍生的造血和间充质干细胞的增殖和分化，在决定外周组织中几种细胞类型的形成中起着关键作用，包括血细胞、脂肪细胞、成骨细胞/破骨细胞和上皮细胞。在这里，我们将回顾这些新发现，它们揭示了 eCB 信号在调节神经系统和外周祖细胞/干细胞命运中的作用。大麻素受体表达和细胞/亚细胞定位的发育调控，以及它们在祖细胞/干细胞生物学中的作用，可能对人类健康和疾病具有重要意义。
