Tech Note: Use of the S2 Genomics Nuclei Debris Removal Stock Reagent

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Single-cell and single-nucleus sequencing techniques have transformed our ability to study the genomics of individual cells, providing insights into the diversity and heterogeneity of biological systems. However, the quality of the cells or nuclei in suspension used to generate a sequencing library can significantly affect the results of these experiments, and in particular, the presence of intracellular and extracellular debris in the sample can have significant adverse effects. The debris can negatively impact the degree of mitochondrial contamination and overall sequencing library quality (genes detected, unique UMIs, percentage of reads mapped to cells, etc). Debris can also lead to clogging of microfluidic channels, high ambient RNA, and background noise leading to diminished data quality. Brain cell or nuclei preparations, for example, can contain high amounts of myelin debris that must be removed, and liver samples may contain high amounts of intracellular debris from hepatocytes containing mitochondria and cellular remnants. To address this issue, we have developed a Nuclei Debris Removal Stock Reagent (100-253-628) that improves the quality of nuclei suspensions prior to sequencing library generation. In this technical note, we describe use of the reagent for cleaning intracellular and extracellular debris from mouse brain and liver nuclei preparations.