Gene Profiling of Human Induced Pluripotent Stem Cell-Derived Astrocyte Progenitors Following Spinal Cord Engraftment
Gene Profiling of Human Induced Pluripotent Stem Cell-Derived Astrocyte Progenitors Following Spinal Cord Engraftment
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DOI：
10.5966/sctm.2013-0153
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发表时间：
2014-05-01
影响因子：
6
通讯作者：
Maragakis, Nicholas J.
中科院分区：
文献类型：
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作者：
Haidet-Phillips, Amanda M.;Roybon, Laurent;Maragakis, Nicholas J.
人类诱导多能干细胞（hiPSC）的产生代表了一个令人兴奋的进步，有望用于干细胞移植治疗以及神经系统疾病建模。基于星形胶质细胞在神经系统疾病中的新兴作用，我们研究了hiPSC衍生的星形胶质细胞祖细胞是否可以移植到啮齿动物脊髓中，以及这些细胞的特征在体外培养和移植到体内脊髓环境后如何变化。我们的研究结果表明，人胚胎干细胞和hiPSC衍生的星形胶质细胞祖细胞在脊髓移植后长期存活，并在体内分化为星形胶质细胞，而其他谱系的细胞很少。移植细胞的基因分析表明星形胶质细胞祖细胞在体内继续成熟，并上调多种星形胶质细胞特异性基因。鉴于这种成熟的星形胶质细胞基因谱，这项工作突出了hiPSC作为一种工具，使用体内疾病建模研究疾病相关的星形胶质细胞生物学，对目前缺乏动物模型的人类神经系统疾病具有重要意义。
The generation of human induced pluripotent stem cells (hiPSCs) represents an exciting advancement with promise for stem cell transplantation therapies as well as for neurological disease modeling. Based on the emerging roles for astrocytes in neurological disorders, we investigated whether hiPSC-derived astrocyte progenitors could be engrafted to the rodent spinal cord and how the characteristics of these cells changed between in vitro culture and after transplantation to the in vivo spinal cord environment. Our results show that human embryonic stem cell- and hiPSC-derived astrocyte progenitors survive long-term after spinal cord engraftment and differentiate to astrocytes in vivo with few cells from other lineages present. Gene profiling of the transplanted cells demonstrates the astrocyte progenitors continue to mature in vivo and upregulate a variety of astrocyte-specific genes. Given this mature astrocyte gene profile, this work highlights hiPSCs as a tool to investigate disease-related astrocyte biology using in vivo disease modeling with significant implications for human neurological diseases currently lacking animal models.