Seitz, B. | bioRxiv Science

bioRxiv2022

Multi-omics analyses identify transcription factor interplay in corneal epithelial fate determination and disease

The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells, while the non-transparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human limbal stem cells from the cornea and keratinocytes from the epidermis, and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors that define specific cell fates, and established their regulatory hierarchy. Single-cell RNA-seq analyses of the cornea and the epidermis confirmed these shared and cell type-specific transcription factors. Notably, the shared and limbal stem cell-specific transcription factors can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the limbal stem cell fate and its association with corneal opacity.

developmental biology↗

bioRxiv2019

A multidimensional framework for measuring biotic novelty: How novel is a community?

Anthropogenic changes in climate, land use and disturbance regimes, as well as introductions of non-native species can lead to the transformation of many ecosystems. The resulting novel ecosystems are usually characterized by species assemblages that have not occurred previously in a given area. Quantifying the ecological novelty of communities (i.e. biotic novelty) would enhance the understanding of environmental change. However, quantification remains challenging since current novelty metrics, such as the number and/or proportion of non-native species in a community, fall short of considering both functional and evolutionary aspects of biotic novelty. Here, we propose the Biotic Novelty Index (BNI), an intuitive and flexible multidimensional measure that combines (1) functional differences between native and non-native introduced species with (2) temporal dynamics of species introductions. We show that the BNI is an additive partition of Raos quadratic entropy, capturing the novel interaction component of the communitys functional diversity. Simulations show that the index varies predictably with the relative amount of functional novelty added by recently arrived species, and they illustrate the need to provide an additional standardized version of the index. We present a detailed R-code and two applications of the BNI by (1) measuring changes of biotic novelty of dry grassland plant communities along an urbanization gradient in a metropolitan region and (2) determining the biotic novelty of plant species assemblages at a national scale. Results illustrate the applicability of the index across scales and its flexibility in the use of data of different quality. Both case studies revealed strong connections between biotic novelty and increasing urbanization, a measure of abiotic novelty. We conclude that the BNI framework may help in building a basis for a better understanding of the ecological and evolutionary consequences of global change.

ecology↗