Failure of bone marrow cells to transdifferentiate into neural cells in vivo
Failure of bone marrow cells to transdifferentiate into neural cells in vivo
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DOI：
10.1126/science.297.5585.1299
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发表时间：
2002-08-23
期刊：
影响因子：
56.9
通讯作者：
Shine, HD
中科院分区：
文献类型：
--
作者：
Castro, RF;Jackson, KA;Shine, HD
有报道表明，成年小鼠骨髓细胞（BMCs）能够在中枢神经系统（CNS）中转分化为具有神经特征的细胞（1,2）。由于整个骨髓中的侧群（SP）细胞是造血干细胞，可以重建BMC群，并能够分化为其他类型的细胞，如心肌细胞和内皮细胞（3-5），我们推测它们也会转分化为神经细胞。为了验证这一点，8只C57Bl/6 （B6）小鼠接受致死剂量的照射，并移植来自Rosa26小鼠的2 103个SP细胞。Rosa26小鼠携带LacZ基因，该基因在大多数细胞（包括神经细胞和SP细胞）中组成性表达，是供体来源细胞的明确标记(6)。移植后10 ~ 12周，80% ~ 95%的受体血细胞为LacZ阳性。移植4个月后，用标准的X-gal细胞组织化学检查两只受体小鼠的中枢神经系统是否有来自Rosa26供体的细胞。在冠状切片（每个大脑50到100个切片，每个大脑超过106个细胞）中，包括嗅球和颈脊髓在内的整个大脑，检测到的唯一半乳糖苷酶（-Gal）阳性细胞是与血管相关的少数细胞。这些gal阳性细胞呈球状形态，没有表明它们是神经细胞的突起
Reports have suggested that adult mouse bone marrow cells (BMCs) are capable of transdifferentiating into cells with neural characteristics in the central nervous system (CNS)(1, 2). Because side-population (SP) cells within whole bone marrow are hematopoietic stem cells that can reconstitute the BMC population and are capable of differentiating into other types of cells such as cardiac myocytes and endothelial cells (3–5), we surmised that they too would transdifferentiate into neural cells.To test this, 8 C57Bl/6 (B6) mice were treated with a lethal dose of irradiation and transplanted with 2 103 SP cells derived from the Rosa26 mouse. The Rosa26 mouse carries the LacZ gene that is constitutively expressed in most cells including neural and SP cells and is an unambiguous marker for donor-derived cells (6). Ten to 12 weeks after transplantation, 80 to 95% of the recipient blood cells were LacZ positive. Four months after transplantation, the CNS of two of the recipient mice were inspected for cells derived from the Rosa26 donor with standard X-gal cytohistochemistry. In coronal sections (50 to 100 sections per brain representing more than 106 cells per brain) taken throughout the full extent of the brain, including the olfactory bulbs and cervical spinal cord, the only-galactosidase (-Gal)–positive cells detected were a few cells (5) that were associated with blood vessels. These-Gal–positive cells had a globular morphology and no processes that would suggest that they were neural