Abstract: An in vitro method is provided for analyzing chromatin accessibility and screening RNA of each single cell in a heterologous population (e.g., a library of cells). The method comprises incubating cell nuclei obtained from lysed cells with a transposome complex in a tagmentation buffer, performing reverse transcription wherein each of the RNAs is reverse transcribed to a DNA barcoded with the first barcode; sequencing DNA, which is extracted from digested cell nuclei; and analyzing chromatin accessibility and RNA of the cells. In a further embodiment, the method described comprises performing combinatorial cellular indexing and/or a perturbation step. Additionally, provided are a transposase TnY, buffer(s), and kit(s) for use in the described method.