Tissue function depends on the proper cellular organization. While the properties of individual cells are increasingly being deciphered using powerful single-cell sequencing technologies, understanding their spatial organization and temporal evolution remains a major challenge. Here, we present Image-seq, a technology that provides single-cell transcriptional data on cells that are isolated from specific spatial positions under image guidance, thus preserving the spatial information of the target cells. It is compatible with in situ and in vivo imaging and can document the temporal and dynamic history of the cells being analyzed. Cell samples are isolated from intact tissue and processed with state-of-the-art library preparation protocols.
The technique, therefore, combines spatial information with highly sensitive RNA sequencing readouts from individual, intact cells. We have used high-throughput, droplet-based sequencing and Smartseq library preparation to demonstrate its application to bone marrow and leukemia biology. We discovered that DPP4 is a highly upregulated gene during early AML progression and marks a more proliferative subpopulation confined to specific bone marrow microenvironments. Furthermore, Image-seq’s ability to isolate viable, intact cells should make it compatible with a range of downstream single-cell analysis tools including multi-omics protocols.
Christa Haase is a postdoctoral research fellow at Harvard Medical School. After obtaining a Bachelor’s and Master’s degree in Chemistry, she went on to pursue a Ph.D. in Physical Chemistry at ETH Zurich and specialized in studying Atomic and Molecular Physics using spectroscopic techniques. During this time in the laboratory of Frédéric Merkt, she developed a novel source of terahertz radiation that could be adjusted throughout the entire range of 0.1-14 THz. She used it to determine the first rotational interval of H2+, which is an important benchmark for theory, in a measurement that was more precise by three orders of magnitude than any other experimental observation at the time. A similar methodology was later used by the Merkt lab to determine the fundamental rotational interval of the helium molecular ion (He2+).
Driven by a desire to develop technologies that better human health, she joined Charles Lin’s laboratory (Harvard Medical School and Massachusetts General Hospital) for her postdoctoral training. There, she developed Image-seq, a technology that provides single-cell transcriptional data on cells that are isolated from specific spatial positions under image guidance. The technique is compatible with intravital microscopy and makes it possible to integrate the spatial, temporal, and molecular information of the target cells. Recently, Christa has become interested in utilizing optogenetic tools to manipulate gene expression and dissect the detailed mechanisms governing inter-cellular communication in vivo.