Genomic and molecular control of cell type and cell type conversions

Abstract

Organisms are made of a limited number of cell types that combine to form higher order tissues and organs. Cell types have traditionally been defined by their morphologies or biological activity, yet the underlying molecular controls of cell type remain unclear. The onset of single cell technologies, and more recently genomics (particularly single cell genomics), has substantially increased the understanding of the concept of cell type, but has also increased the complexity of this understanding. These new technologies have added a new genome wide molecular dimension to the description of cell type, with genome-wide expression and epigenetic data acting as a cell type ‘fingerprint’ to describe the cell state. Using these genomic fingerprints cell types are being increasingly defined based on specific genomic and molecular criteria, without necessarily a distinct biological function. In this review, we will discuss the molecular definitions of cell types and cell type control, and particularly how endogenous and exogenous transcription factors can control cell types and cell type conversions.

Topography-dependent gene expression and function of common cell archetypes in large and small porcine airways

“…Cells with similar morphology and canonical gene expression biomarkers are generally assigned the same cell identity, but their gene expression profile and physiology may vary because: 1) transcriptional regulation is modulated by the cellular microenvironment, with cells having a location-dependent gene expression profile, or 2) the developmental origin and history of two seemingly identical cells may differ, which would likely affect their expression profile and function (Fu et al, 2017; Morrisey et al, 2013; Rao et al, 2020; Wang et al, 2019; Wang et al, 2015; Xian et al, 2018; Zuo et al, 2015).…”

“…A cell with similar morphology and marker gene expression may vary in its transcriptome and function due to its environment, or due to its developmental history (Fu et al, 2017;Morrisey et al, 2013;Rao et al, 2020;Wang et al, 2019;Wang et al, 2015;Xian et al, 2018;Zuo et al, 2015). Whereas our experiments were not designed to Volcano plots and top twenty cell-specific differentially expressed genes in basal, secretory, and ciliated large and small airway epithelia.…”

Computational Methods for Mapping, Assembly and Quantification for Coding and Non-coding Transcripts

“…We have mostly discussed bulk RNA-Seq in this review, but cells are heterogeneous mixtures. Single cell RNA-Seq is revealing more heterogeneity in gene expression than expected [ 177 , 178 ], which is challenging traditional definitions of cell type [ 179 , 180 ]. Overall, expression quantification and particularly RNA-Seq is a powerful technique that has led to major insights into biological processes, and has become a key tool for solving future biomedical problems.…”

Chromatin and Epigenetic Rearrangements in Embryonic Stem Cell Fate Transitions

“…These epigenetic barriers can resist all cell type conversions but can also act as bidirectional valves, guiding cells toward a differentiated cell type but then blocking reversion to progenitor cells and locking cells into a fixed cell type ( Arabaci et al, 2020 ). Epigenetic control is mediated by DNA-binding proteins, particularly transcription factors (TFs) ( Fu et al, 2017 ), that recruit epigenetic enzymes to regulate chemical modifications on DNA and histones and reshape or remodel chromatin structure. This process both responds to cell type changes and controls them and is critical in normal developmental processes.…”