Hematopoietic progenitors express neural genes
Hematopoietic progenitors express neural genes
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DOI：
10.1073/pnas.2434383100
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发表时间：
2003-12-09
影响因子：
11.1
通讯作者：
Trisler, D
中科院分区：
文献类型：
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作者：
Goolsby, J;Marty, MC;Trisler, D
最近有报道称，骨髓或从骨髓中选择的细胞在体外用神经诱导因子处理或送入大脑后产生具有神经表型的细胞。然而，我们之前发现未经处理的骨髓细胞表达神经髓鞘碱性蛋白基因的产物，并且我们在这里证明了一个体外骨髓细胞亚群表达神经原性转录因子Pax-6以及编码神经丝H、NeuN（神经元核蛋白）、HuC/HuD（胡抗原C/胡抗原ID）和GAD65（谷氨酸脱羧酶65）的神经元基因。以及编码CNPase（2‘,3’环核3'-磷酸水解酶）的少突胶质基因。星形胶质胶质原纤维酸性蛋白（GFAP）未检出。这些细胞也是CD34(+)，一种造血干细胞的标记物。这些来自成年小鼠骨髓的高度增殖的CD34（+）细胞的培养，一致显示出与造血祖细胞（CD45（+）、CD34（+）、Sca-1（+）、AA4.1（+）、cKit（+）、GATA-2（+）和LMO-2(+)）相当的表型。体外骨髓中表达的神经元和少突胶质基因在所有培养的CD34（+）细胞中也有表达，未观察到GFAP。在CD34（+）细胞移植到成人大脑后，神经元或少突胶质标记物分离成不同的非重叠细胞群，而星形胶质GFAP在没有其他神经标记物的情况下出现在一组单独的植入细胞中。因此，神经元和少突胶质基因产物存在于骨髓细胞的一个亚群中，这些基因的表达可以在大脑中被调节。这些CD34（+）细胞也表达在早期发育中发现的转录因子（Rex-1和Oct-4），这一事实引出了它们可能是多能胚胎样干细胞的假设。
Bone marrow, or cells selected from bone marrow, were reported recently to give rise to cells with a neural phenotype after in vitro treatment with neural-inducing factors or after delivery into the brain. However, we showed previously that untreated bone marrow cells express products of the neural myelin basic protein gene, and we demonstrate here that a subset of ex vivo bone marrow cells expresses the neurogenic transcription factor Pax-6 as well as neuronal genes encoding neurofilament H, NeuN (neuronal nuclear protein), HuC/HuD (Hu-antigen C/Hu-antigen ID), and GAD65 (glutamic acid decarboxylase 65), as well as the oligodendroglial gene encoding CNPase (2',3' cyclic nucleoticle 3'-phosphohydrolase). In contrast, astroglial glial fibrillary acidic protein (GFAP) was not detected. These cells also were CD34(+), a marker of hematopoietic stem cells. Cultures of these highly proliferative CD34(+) cells, derived from adult mouse bone marrow, uniformly displayed a phenotype comparable with that of hematopoietic progenitor cells (CD45(+), CD34(+), Sca-1(+), AA4.1(+), cKit(+), GATA-2(+), and LMO-2(+)). The neuronal and oligodendroglial genes expressed in ex vivo bone marrow also were expressed in all cultured CD34(+) cells, and GFAP was not observed. After CD34(+) cell transplantation into adult brain, neuronal or oligodendroglial markers segregated into distinct nonoverlapping cell populations, whereas astroglial GFAP appeared, in the absence of other neural markers, in a separate set of implanted cells.. Thus, neuronal and oligodendroglial gene products are present in a subset of bone marrow cells, and the expression of these genes can be regulated in brain. The fact that these CD34(+) cells also express transcription factors (Rex-1 and Oct-4) that are found in early development elicits the hypothesis that they may be pluripotent embryonic-like stem cells.