Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells.
Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells.
复制标题
个体长期造血干细胞的超高频重编程产生低体细胞变异诱导多能干细胞。
DOI：
10.1016/j.celrep.2019.02.021
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Bouhassira,EricE
中科院分区：
文献类型：
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作者：
Wang,Kai;Guzman,AnthonyK;Yan,Zi;Zhang,Shouping;Hu,MichaelY;Hamaneh,MehdiB;Yu,Yi-Kuo;Tolu,Seda;Zhang,Jinghang;Kanavy,HollyE;Ye,Kenny;Bartholdy,Boris;Bouhassira,EricE
将人类细胞重编程为诱导多能干细胞（iPSC）的效率仍然很低。我们报告说，个别成年人CD 49 f+长期造血干细胞（LT-HSC）可以重新编程为iPSC在接近50%的效率使用仙台病毒转导。这种对重编程的敏感性是LT-HSC特有的，因为它在定向祖细胞中逐渐降低。LT-HSC重编程可以遵循多个路径，并且当在细胞已经退出G 0之后进行转导时最有效。对从9名个体收集的75对皮肤成纤维细胞/LT-HSC样本进行测序显示，LT-HSC含有比皮肤成纤维细胞更低的体细胞单核苷酸变体（SNV）和插入缺失负荷，并且每年积累约12个SNV。突变分析显示，LT-HSC和成纤维细胞具有非常不同的体细胞突变特征，并且iPSC中的体细胞突变通常在重编程之前存在。LT-HSC可能成为生产临床级iPSC的首选细胞来源。
Efficiency of reprogramming of human cells into induced pluripotent stem cells (iPSCs) has remained low. We report that individual adult human CD49f+long-term hematopoietic stem cells (LT-HSCs) can be reprogrammed into iPSCs at close to 50% efficiency using Sendai virus transduction. This exquisite sensitivity to reprogramming is specific to LT-HSCs, since it progressively decreases in committed progenitors. LT-HSC reprogramming can follow multiple paths and is most efficient when transduction is performed after the cells have exited G0. Sequencing of 75 paired skin fibroblasts/LT-HSC samples collected from nine individuals revealed that LT-HSCs contain a lower load of somatic single-nucleotide variants (SNVs) and indels than skin fibroblasts and accumulate about 12 SNVs/year. Mutation analysis revealed that LT-HSCs and fibroblasts have very different somatic mutation signatures and that somatic mutations in iPSCs generally exist prior to reprogramming. LT-HSCs may become the preferred cell source for the production of clinical-grade iPSCs.