Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells

Abstract

Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single-cell RNA-seq data with a simple metric. This metric can detect exclusivity independently of the mean value and the monoallelic nature of gene expression. Chromosomal segments and gene families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.

Variability of the innate immune response is globally constrained by transcriptional bursting

“…A better understanding of the relationships, and in particular mechanistic basics for controlling gene-specific slopes (i.e., response variability) as well as their sensitivity to pharmacological perturbation and infection and disease state, will require further detailed investigations ( Robles-Rebollo et al, 2022 ). Nevertheless, we believe that our methodology, relying on the inference of mean-variance relationships, provides new insight into regulation of single-cell variability of innate immune signalling and will be applicable to other gene expression systems, including prominent stochastic regulation of adaptive immunity ( de la Higuera et al, 2019 ; Iakovlev et al, 2021 ).…”

“…The patterns of temporal mRNA production in a single cell, and the overall mRNA (and protein) distribution in cellular populations, are controlled by transcriptional bursting, namely, via the modulation of burst size and burst frequency ( Raj et al, 2006 ; Suter et al, 2011 ; Molina et al, 2013 ). The innate and adaptive immune responses exhibit extreme variability at the single cell level, in comparison to other tissue systems ( Shalek et al, 2013 ; Shalek et al, 2014 ; Hagai et al, 2018 ), where only subsets of cells produce specific effector molecules, and thus are able to respond to pathogen ( Avraham et al, 2015 ; Iakovlev et al, 2021 ). This apparent level of variability poses a fundamental systems biology question; how do robust immune responses emerge from this heterogeneous transcriptional bursting process?…”

Artificial neural network‐based gene screening and immune cell infiltration analysis of osteosarcoma feature

“…In the event that the upregulated gene expression level exceeded the median, it was assigned a score of 1; otherwise, it was scored 0. If the downregulated gene expression level was below the median, it was scored 1; otherwise, it was marked as 0 37,38 . This process resulted in a matrix comprising all gene scores for CDEGs.…”

“…If the downregulated gene expression level was below the median, it was scored 1; otherwise, it was marked as 0. 37,38 This process resulted in a matrix comprising all gene scores for CDEGs.…”

May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression

“…It has also been shown to increase stringency of synaptic partnerships in other areas of the brain ( Garrett et al, 2018 ). However, a recent analysis found that mammalian DSCAM and DSCAML1, along with other members of the basigin-related family, are sometimes expressed in a mutually exclusive pattern ( Iakovlev et al, 2021 ). It is therefore possible that DSCAM genes also contribute to non-deterministic aspects of cell identity in mammals.…”