Image-seq: spatially resolved single-cell sequencing guided by in situ and in vivo imaging

Tissue function depends on cellular organization. While single-cell sequencing technologies decipher individual cell properties, understanding spatial organization and temporal evolution remains challenging. Image-seq provides single-cell transcriptional data from specific spatial locations under image guidance, preserving spatial information. Compatible with in situ and in vivo imaging, it documents temporal cell history. Cells are isolated from intact tissue and processed with advanced library preparation protocols, combining spatial information with sensitive RNA sequencing readouts. Applications in bone marrow and leukemia biology are demonstrated, revealing DPP4 upregulation during early acute myeloid leukemia progression, marking a proliferative subpopulation in specific bone marrow microenvironments. Image-seq's ability to isolate viable cells enables compatibility with downstream single-cell analysis tools, including multi-omics protocols.

Christa Haase, Karin Gustafsson, Shenglin Mei, Shu-Chi Yeh, Dmitry Richter, Jelena Milosevic, Raphaël Turcotte, Peter V. Kharchenko, David B. Sykes, David T. Scadden, Charles P. Lin