Prospective identification and isolation of enteric nervous system progenitors using Sox2.
Prospective identification and isolation of enteric nervous system progenitors using Sox2.
复制标题
DOI：
10.1002/stem.557
复制
发表时间：
2011-01
期刊：
影响因子：
5.2
通讯作者：
Pachnis, Vassilis
中科院分区：
文献类型：
--
作者：
Heanue, Tiffany A.;Pachnis, Vassilis
从发育和成熟的组织中鉴定和分离谱系特异性祖细胞的能力将使得能够开发用于疾病治疗的细胞替代疗法。肠神经系统（ENS）调节重要的肠道功能，包括控制蠕动肌肉收缩，并且由含有神经元和神经胶质细胞的互连神经节组成。先天性巨结肠（HSCR）是影响ENS的最常见和最好理解的疾病之一，其特征在于由于神经嵴祖细胞的肠道定殖缺陷而导致远端肠道缺乏肠神经节，并且是未来细胞替代疗法的极好候选者。我们以前的微阵列实验确定了神经祖细胞和干细胞标记SRY相关同源框转录因子2（Sox 2）在胚胎ENS. We现在表明，Sox 2在ENS从胚胎到成人阶段的表达，并构成了一个新的标记ENS祖细胞及其神经胶质细胞衍生物。我们还表明，Sox 2的表达与SOX 10，ENS祖细胞和肠神经胶质细胞的一个公认的标志物显着重叠。我们已经开发了一种策略来选择表达Sox 2的细胞，通过对来自Sox 2 βgeo/+小鼠胚胎的培养肠道细胞使用G418选择，从而允许新霉素抗性Sox 2表达细胞的大量富集和扩增。Sox 2 βgeo细胞培养物富集ENS祖细胞。移植到胚胎小鼠肠道后，Sox 2 βgeo细胞迁移、分化并与内源性ENS丛共定位。我们的研究将促进动物模型中细胞替代策略的发展，这对于开发HSCR的人类细胞替代疗法至关重要。干细胞2011;29：128-140
The capacity to identify and isolate lineage-specific progenitor cells from developing and mature tissues would enable the development of cell replacement therapies for disease treatment. The enteric nervous system (ENS) regulates important gut functions, including controlling peristaltic muscular contractions, and consists of interconnected ganglia containing neurons and glial cells. Hirschsprung's disease (HSCR), one of the most common and best understood diseases affecting the ENS, is characterized by absence of enteric ganglia from the distal gut due to defects in gut colonization by neural crest progenitor cells and is an excellent candidate for future cell replacement therapies. Our previous microarray experiments identified the neural progenitor and stem cell marker SRY-related homoebox transcription factor 2 (Sox2) as expressed in the embryonic ENS. We now show that Sox2 is expressed in the ENS from embryonic to adult stages and constitutes a novel marker of ENS progenitor cells and their glial cell derivatives. We also show that Sox2 expression overlaps significantly with SOX10, a well-established marker of ENS progenitors and enteric glial cells. We have developed a strategy to select cells expressing Sox2, by using G418 selection on cultured gut cells derived from Sox2βgeo/+ mouse embryos, thus allowing substantial enrichment and expansion of neomycin-resistant Sox2-expressing cells. Sox2βgeo cell cultures are enriched for ENS progenitors. Following transplantation into embryonic mouse gut, Sox2βgeo cells migrate, differentiate, and colocalize with the endogenous ENS plexus. Our studies will facilitate development of cell replacement strategies in animal models, critical to develop human cell replacement therapies for HSCR. Stem Cells 2011;29:128–140
登录
查看更多内容
影响因子：
5.3
作者：
Kuhlbrodt, K;Herbarth, B;Wegner, M
通讯作者：
Wegner, M
影响因子：
2.4
作者：
Baillie, CT;Kenny, SE;Lloyd, DA
通讯作者：
Lloyd, DA
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
5.3
作者：
Aquino, JB;Hjerling-Leffler, J;Ernfors, P
通讯作者：
Ernfors, P
影响因子：
2.7
作者：
Denaxa, Myrto;Sharpe, Paul T.;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis