Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors.
Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors.
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DOI：
10.1016/j.exphem.2017.09.003
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发表时间：
2018-01
影响因子：
2.6
通讯作者：
Howe SJ
中科院分区：
文献类型：
--
作者：
Alonso-Ferrero ME;van Til NP;Bartolovic K;Mata MF;Wagemaker G;Moulding D;Williams DA;Kinnon C;Waddington SN;Milsom MD;Howe SJ
整合缺陷型载体（IdLV）在分裂的干细胞中瞬时表达基因。造血干/祖细胞（HSPC）可以使用IdLV编程。来自IdLV的H 0XB 4或Angptl 3表达改善了移植的HSPC的植入。短期基因递送避免了与组成型表达相关的副作用。整合缺陷型慢病毒（IdLV）将基因有效地递送到组织中，但从分裂的细胞中迅速丢失。这种特性可以被用来瞬时表达转基因以操纵细胞生物学。在此，我们证明了短期基因表达在移植期间通过使用IdLV递送HOXB 4和Angptl 3以增强造血干细胞和祖细胞（HSPC）的植入来改善HSPC的功能效力的效用。这些基因中的任一个的组成性过表达可能是不期望的，但是IdLV的瞬时性质降低了这种风险以及与子细胞中的主动基因表达相关的风险。瞬时表达导致体内竞争性再增殖试验中多系造血移植增加，而没有组成性过表达模型中报告的副作用。成人干细胞的命运还没有编程以前使用IdLVs，但我们证明，这些瞬时基因表达工具可以产生临床相关的改变或应用于调查基础生物学。
Integration-deficient vectors (IdLVs) express genes transiently in dividing stem cells. Hematopoietic stem/progenitor cells (HSPCs) can be programmed using IdLVs. HOXB4 or Angptl3 expression from IdLVs improves engraftment of transplanted HSPCs. Short-term gene delivery avoids the side effects associated with constitutive expression. Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells. Transient expression led to increased multilineage hematopoietic engraftment in in vivo competitive repopulation assays without the side effects reported in constitutive overexpression models. Adult stem cell fate has not been programmed previously using IdLVs, but we demonstrate that these transient gene expression tools can produce clinically relevant alterations or be applied to investigate basic biology.
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影响因子：
2.6
作者：
Chou, Song;Flygare, Johan;Lodish, Harvey F.
通讯作者：
Lodish, Harvey F.
影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.7
作者：
Kaplan, David;Kaye, Nicholas;Lazarus, Hillard M.
通讯作者：
Lazarus, Hillard M.
影响因子：
5.1
作者：
Schott, J. W.;Hoffmann, D.;Schambach, A.
通讯作者：
Schambach, A.
影响因子：
3.7
作者：
Farahbakhshian E;Verstegen MM;Visser TP;Kheradmandkia S;Geerts D;Arshad S;Riaz N;Grosveld F;van Til NP;Meijerink JP
通讯作者：
Meijerink JP