Scientists develop new 'DARLIN' mouse model with high clonal barcode diversity

Scientists have developed a new mouse model with a high clonal barcode diversity for joint lineage, transcriptomic, and epigenomic profiling in single cells, according to a report published by bioRxiv on Jan. 31.

Boston Children's Hospital's Fernando Camargo and Westlake University's Shou-Wen Wang, alongside their teams, have developed a new Cas9 barcoding mouse line named DARLIN that has the potential to greatly change the study of tissue development and homeostasis. 

The current models have limited barcode diversity, restricting their use in tissues made up of millions of cells; however, DARLIN offers improved barcode diversity, with an estimated ~1018 lineage barcodes across tissues. It also utilizes terminal deoxynucleotidyl transferase (TdT) to enhance insertion events over 30 CRISPR target sites, steadily integrating into three distinct genomic loci.

DARLIN is inducible and can enable the detection of usable barcodes in  ~60% of studied single cells, making it a crucial tool for examining fate priming within developing hematopoietic stem cells (HSCs) and revealing the unusual aspects of HSC migration. 

Furthermore, using DARLIN, the scientists have adapted a method jointly profiling DNA methylation, chromatin accessibility, gene expression and lineage information.

The development of DARLIN is considered exciting by scientists due to its potential to enable the widespread high-resolution study of lineage relationships and their molecular signatures in diverse tissues and physiological contexts.