9月13日,日本理化研究所發(fā)布新聞公報(bào)稱,，該所研究人員成功誘導(dǎo)小鼠胚胎干細(xì)胞，有選擇性地分化成小腦神經(jīng)細(xì)胞,，且實(shí)現(xiàn)了較高的分化效率,。
公報(bào)說,，小腦皮質(zhì)中層內(nèi)的浦肯雅細(xì)胞是掌管精確運(yùn)動(dòng)和學(xué)習(xí)的主要神經(jīng)細(xì)胞,，在醫(yī)學(xué)方面具有相當(dāng)重要的作用,，以往誘導(dǎo)胚胎干細(xì)胞有選擇性地分化成浦肯雅細(xì)胞的方法效率低下，只有約0．5％的胚胎干細(xì)胞最終能分化成浦肯雅細(xì)胞,。
理化研究所發(fā)展生物學(xué)研究中心的研究小組,，改進(jìn)了此前培育大腦神經(jīng)細(xì)胞的無血清浮游培養(yǎng)法，開發(fā)出一種能在試管內(nèi)再現(xiàn)胚胎發(fā)育過程中小腦發(fā)育環(huán)境的新方法,。
在實(shí)驗(yàn)中用這種方法誘導(dǎo)小鼠胚胎干細(xì)胞分化時(shí),，約80％的胚胎干細(xì)胞分化成了浦肯雅細(xì)胞的祖細(xì)胞，這其中又有約30％的祖細(xì)胞最后形成了浦肯雅細(xì)胞,。將如此分化形成的細(xì)胞在試管中培育一段時(shí)間后,，通過電生理學(xué)分析，研究人員觀察到這些細(xì)胞擁有浦肯雅細(xì)胞特有的神經(jīng)活動(dòng),，從而證實(shí)這些細(xì)胞確實(shí)具備浦肯雅細(xì)胞的功能,。
在移植實(shí)驗(yàn)中，研究人員將提純后的浦肯雅細(xì)胞的祖細(xì)胞,，移植入小鼠胚胎的小腦中,，移植細(xì)胞順利“扎根”在小腦的浦肯雅細(xì)胞層中，并正確融入小腦回路,。
公報(bào)說,，脊髓小腦變性癥是小腦神經(jīng)細(xì)胞因逐漸萎縮、死亡而數(shù)量減少導(dǎo)致的疾病,，這項(xiàng)成果為此類疾病的病理研究和開發(fā)新療法提供了新途徑,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature Neuroscience doi:10.1038/nn.2638
Ontogeny-recapitulating generation and tissue integration of ES cell–derived Purkinje cells
Keiko Muguruma,Ayaka Nishiyama,Yuichi Ono,Hiroyuki Miyawaki,Eri Mizuhara,Seiji Hori,Akira Kakizuka,Kunihiko Obata,Yuchio Yanagawa,Tomoo Hirano& Yoshiki Sasai
Purkinje cells are the sole output neurons of the cerebellar cortex and their dysfunction causes severe ataxia. We found that Purkinje cells could be robustly generated from mouse embryonic stem (ES) cells by recapitulating the self-inductive signaling microenvironments of the isthmic organizer. The cell-surface marker Neph3 enabled us to carry out timed prospective selection of Purkinje cell progenitors, which generated morphologically characteristic neurons with highly arborized dendrites that expressed mature Purkinje cell–specific markers such as the glutamate receptor subunit GluRδ2. Similar to mature Purkinje cells, these neurons also showed characteristic spontaneous and repeated action potentials and their postsynaptic excitatory potentials were generated exclusively through nonNMDA glutamate receptors. Fetal transplantation of precursors isolated by fluorescence-activated cell sorting showed orthotopic integration of the grafted neurons into the Purkinje cell layer with their axons extending to the deep cerebellar nuclei and dendrites receiving climbing and parallel fibers. This selective preparation of bona fide Purkinje cells should aid future investigation of this important neuron.
