Tracking organoid cell fate dynamics in space and time

Abstract

Throughout the lifetime of living systems, tissue homeostasis and renewal constantly take place to confront challenging conditions, both internally, such as cell aging, and externally, such as infections, so that health can be maintained. Such processes require a tight balance between cell proliferation and differentiation. When homeostasis is disturbed, diseases like cancer can develop. Therefore, understanding the regulation of tissue homeostasis is a key question in biology. However, directly monitoring the dynamics of proliferation and differentiation in live animals remains extremely challenging. Common methods, such as immunostaining and single-cell RNA sequencing, require killing the animal and fixing the cells. Therefore, they can merely provide information in a single time frame. As a result, lineage tracing techniques are introduced, where cells are labeled with a heritable marker that can be detected in progeny after a certain period by fluorescence microscopy or sequencing. Nevertheless, they only produce lineage dynamics indirectly.