The invention discloses a low-abundance
cell nucleus enrichment method which comprises the following steps: (1) splitting a
tissue sample to obtain a
cell nucleus with
extracellular cytoplasm retained; and (2) marking and sorting the
cell nucleuses obtained in the step (1) to obtain enriched low-abundance cell nucleuses. According to the method, a mild dissociation technology is used, so that more
cytoplasm components can be reserved in cell nucleuses, and then the cell nucleuses are used for marking
cytoplasm proteins and are combined with
flow sorting, so that directional enrichment of the cell nucleuses with low abundance and specific functional states can be effectively realized. Through the whole
process optimization, the method can ensure the completeness of the
cell nucleus to the maximum extent, takes downstream sequencing application into consideration, and can obtain high-quality mononuclear
transcriptome sequencing data by combining with the screening of cytoplasm
sequencing data. Moreover, according to the method, directional enrichment is realized through the
cytoplasmic protein, the use cost can be effectively reduced, and the method is suitable for large-scale clinical sample
data acquisition and has higher flux compared with a single space
transcriptome slice.