使用CRISPR-Cas9改造的小鼠细胞系可同时获得小鼠单细胞谱系史和基因表达谱，这一成果由美国波士顿儿童医院Fernando D. Camargo和波士顿达纳-法伯癌症研究所Sahand Hormoz研究组合作取得。2020年5月14日出版的《细胞》杂志在线发表了这一研究成果。

研究人员建立了CRISPR阵列修复谱系追踪（CARLIN）的小鼠细胞系和相应的分析工具，可用于同时获得体内单个细胞的谱系和转录组信息。该方法可利用CRISPR技术在发育或成年期的任何时期以可诱导的方式生成44,000多个转录条形码，其与顺序条形码兼容并且具有完全确定的遗传信息。

研究人员已利用CARLIN鉴定了胎儿肝造血干细胞（HSC）克隆活动中的内在偏好性，并揭示了HSC对损伤反应中先前未知的克隆瓶颈。CARLIN还可以在不进行细胞分选的情况下，无偏倚地鉴定与HSC活性相关的转录标记。

据悉，追踪细胞的谱系史是回答生物学上各种基本问题的关键。细胞谱系信息与其它分子特征的耦合是该领域研究的重要目标。

附：英文原文

Title: An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells

Author: Sarah Bowling, Duluxan Sritharan, Fernando G. Osorio, Maximilian Nguyen, Priscilla Cheung, Alejo Rodriguez-Fraticelli, Sachin Patel, Wei-Chien Yuan, Yuko Fujiwara, Bin E. Li, Stuart H. Orkin, Sahand Hormoz, Fernando D. Camargo

Issue&Volume: 2020-05-14

Abstract: Tracing the lineage history of cells is key to answering diverse and fundamental questionsin biology. Coupling of cell ancestry information with other molecular readouts representsan important goal in the field. Here, we describe the CRISPR array repair lineagetracing (CARLIN) mouse line and corresponding analysis tools that can be used to simultaneouslyinterrogate the lineage and transcriptomic information of single cells in vivo. This model exploits CRISPR technology to generate up to 44,000 transcribed barcodesin an inducible fashion at any point during development or adulthood, is compatiblewith sequential barcoding, and is fully genetically defined. We have used CARLIN toidentify intrinsic biases in the activity of fetal liver hematopoietic stem cell (HSC)clones and to uncover a previously unappreciated clonal bottleneck in the responseof HSCs to injury. CARLIN also allows the unbiased identification of transcriptionalsignatures associated with HSC activity without cell sorting.

DOI: 10.1016/j.cell.2020.04.048

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30554-7