Exploiting Single-Cell Tools in Gene and Cell Therapy.
Exploiting Single-Cell Tools in Gene and Cell Therapy.
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DOI：
10.3389/fimmu.2021.702636
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kent DG
中科院分区：
文献类型：
--
作者：
Bode D;Cull AH;Rubio-Lara JA;Kent DG
在过去的五年里，随着测序成本的持续下降以及大量分子检测与测序读数的结合，单细胞分子工具以令人难以置信的速度发展。这一快速的技术发展时期促进了对个体分子特征的描述，包括个体细胞的基因组、转录组、表观基因组和蛋白质组，从而使控制复杂生物系统的分子网络获得了前所未有的分辨率。通过在干细胞生物学、免疫学和肿瘤细胞生物学等以细胞异质性为关键特征的系统中的工作，单细胞分子筛选的巨大力量得到了特别强调。单细胞组学技术已经有助于识别新的疾病生物标志物、细胞亚群、治疗靶点和诊断方法，其中许多是批量测序方法无法检测到的。最近，将单细胞多组学与单细胞功能输出和/或物理位置整合的努力一直具有挑战性，但已取得了实质性进展。也许最令人兴奋的是，随着通过 CRISPR 技术调节细胞的最新进展，特别是碱基编辑器的发展，出现了超越静态细胞状态描述的新机会，这大大提高了细胞和基因治疗的前景。在这篇综述中，我们简要概述了新兴的单细胞技术，并讨论了整合单细胞分子筛选和执行单细胞多组学临床应用的当前发展。我们还讨论了如何将单细胞分子测定与功能数据有效地结合起来，以揭示细胞决策的机制。最后，我们反思了空间转录组学和蛋白质组学的介绍、其与单细胞 RNA 测序 (scRNA-seq) 的互补作用以及在细胞和基因治疗中的潜在应用。
Single-cell molecular tools have been developed at an incredible pace over the last five years as sequencing costs continue to drop and numerous molecular assays have been coupled to sequencing readouts. This rapid period of technological development has facilitated the delineation of individual molecular characteristics including the genome, transcriptome, epigenome, and proteome of individual cells, leading to an unprecedented resolution of the molecular networks governing complex biological systems. The immense power of single-cell molecular screens has been particularly highlighted through work in systems where cellular heterogeneity is a key feature, such as stem cell biology, immunology, and tumor cell biology. Single-cell-omics technologies have already contributed to the identification of novel disease biomarkers, cellular subsets, therapeutic targets and diagnostics, many of which would have been undetectable by bulk sequencing approaches. More recently, efforts to integrate single-cell multi-omics with single cell functional output and/or physical location have been challenging but have led to substantial advances. Perhaps most excitingly, there are emerging opportunities to reach beyond the description of static cellular states with recent advances in modulation of cells through CRISPR technology, in particular with the development of base editors which greatly raises the prospect of cell and gene therapies. In this review, we provide a brief overview of emerging single-cell technologies and discuss current developments in integrating single-cell molecular screens and performing single-cell multi-omics for clinical applications. We also discuss how single-cell molecular assays can be usefully combined with functional data to unpick the mechanism of cellular decision-making. Finally, we reflect upon the introduction of spatial transcriptomics and proteomics, its complementary role with single-cell RNA sequencing (scRNA-seq) and potential application in cellular and gene therapy.
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影响因子：
48
作者：
Angermueller C;Clark SJ;Lee HJ;Macaulay IC;Teng MJ;Hu TX;Krueger F;Smallwood S;Ponting CP;Voet T;Kelsey G;Stegle O;Reik W
通讯作者：
Reik W
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.5
作者：
Asp, Michaela;Giacomello, Stefania;Lundeberg, Joakim
通讯作者：
Lundeberg, Joakim
DOI：
10.1007/978-1-4939-1133-2_22
发表时间：
2014-01-01
期刊：
HEMATOPOIETIC STEM CELL PROTOCOLS, 3RD EDITION
影响因子：
--
作者：
Beard, Brian C.;Adair, Jennifer E.;Kiem, Hans-Peter
通讯作者：
Kiem, Hans-Peter
影响因子：
4.6
作者：
Bhagwat N;Dulmage K;Pletcher CH Jr;Wang L;DeMuth W;Sen M;Balli D;Yee SS;Sa S;Tong F;Yu L;Moore JS;Stanger BZ;Dixon EP;Carpenter EL
通讯作者：
Carpenter EL