Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
PLoS One. 2010 Jan 21;5(1):e8814. doi: 10.1371/journal.pone.0008814.
The question of whether intact somatic cells committed to a specific differentiation fate, can be reprogrammed in vivo by exposing them to a different host microenvironment is a matter of controversy. Many reports on transdifferentiation could be explained by fusion with host cells or reflect intrinsic heterogeneity of the donor cell population.
METHODOLOGY/PRINCIPAL FINDINGS: We have tested the capacity of cloned populations of mouse and human muscle progenitor cells, committed to the myogenic pathway, to transdifferentiate to neurons, following their inoculation into the developing brain of newborn mice. Both cell types migrated into various brain regions, and a fraction of them gained a neuronal morphology and expressed neuronal or glial markers. Likewise, inoculated cloned human myogenic cells expressed a human specific neurofilament protein. Brain injected donor cells that expressed a YFP transgene controlled by a neuronal specific promoter, were isolated by FACS. The isolated cells had a wild-type diploid DNA content.
These and other results indicate a genuine transdifferentiation phenomenon induced by the host brain microenvironment and not by fusion with host cells. The results may potentially be relevant to the prospect of autologous cell therapy approach for CNS diseases.
关于完整的体细胞在特定分化命运下，是否可以通过暴露于不同的宿主微环境在体内被重新编程，这是一个有争议的问题。许多关于转分化的报告可以通过与宿主细胞融合来解释，或者反映供体细胞群体的固有异质性。
方法/主要发现：我们已经测试了克隆的小鼠和人类肌肉祖细胞群体的能力，这些细胞群已经朝着成肌途径分化，在将其接种到新生小鼠的发育大脑后，它们可以向神经元转分化。两种细胞类型都迁移到大脑的各个区域，其中一部分获得神经元形态并表达神经元或神经胶质标记物。同样，接种的克隆人类肌肉细胞表达了人类特异性神经丝蛋白。通过流式细胞术分离出表达由神经元特异性启动子控制的 YFP 转基因的脑内注射供体细胞。分离出的细胞具有野生型二倍体 DNA 含量。
这些和其他结果表明，宿主大脑微环境诱导了真正的转分化现象，而不是通过与宿主细胞融合。这些结果可能与 CNS 疾病的自体细胞治疗方法的前景有关。
