Spatial Analysis of Single Fiber Cells of the Developing Ocular Lens Reveals Regulated Heterogeneity of Gene Expression

Abstract

The developing eye lens presents an exceptional paradigm for spatial transcriptomics. It is composed of highly organized long, slender transparent fiber cells, which differentiate from the edges of the anterior epithelium of the lens (equator), attended by high expression of crystallins, which generate transparency. Every fiber cell, therefore, is an optical unit whose refractive properties derive from its gene activity. Here, we probe this tangible relationship between the gene activity and the phenotype by studying the expression of all known 17 crystallins and 77 other non-crystallin genes in single fiber cells isolated from three states/regions of differentiation allowing us to follow the progression of differentiation at the single cell level. The data demonstrates highly variable gene activity, in cortical fibers, interposed between the nascent and the terminally differentiated fiber-cell transcription. This data suggests that the so-called “Stochastic”, highly heterogeneous gene activity is a regulated intermediate in the progression towards the realization of a functional phenotype.