Geohash Barcoding: a novel single cell spatial toolbox to decipher malignancy through epigenetic regulation and genome instability crosstalk with the tumor microenvironment

Nonmutational epigenetic reprogramming and genome instability are two important hallmarks of cancer.

To fully comprehend malignancy, it is essential to determine how these two hallmarks are connected and interact with the tumor microenvironment in a mechanistic manner.

The epithelial-mesenchymal transition (EMT) plays a crucial role in initiating metastasis, and tumor relapse, which occurs in the majority of tumor types, remains a major clinical challenge.

Hence, understanding the control of EMT and tumor relapse through epigenetic and genome instability crosstalk with the tumor microenvironment at the single-cell level in the context of the tumor will provide us with a better understanding of malignancy. However, no tools currently exist that allow for this complex analysis.

To this end, we plan to develop an interdisciplinary toolbox, termed Geohash barcoding, for measuring single-cell spatial epigenetics, genome instability, and tumor microenvironment by combining the Geohash system, digital light processing, photo-cleavable chemicals, DNA oligo indexing, and bioengineering proteins.

We will also use Geohash barcoding to study EMT control and tumor relapse in human colorectal cancer. Our novel toolbox has the potential to revolutionize both basic and translational medical research.

The results from this project will significantly advance our understanding of the complex interplay between epigenetic, genome instability, and the tumor microenvironment in malignancy.