Bioinformatic and Genomic Analyses of Cellular Reprogramming and Direct Lineage Conversion

Abstract

Cellular reprogramming, whereby cell fate can be changed by the expression of a few defined factors, is a remarkable process that harnesses the innate ability of a cell's own genome to rework its expressional networks and function. Since cell lineages are defined by global regulation of gene expression, transcriptional regulators, and coupled to the epigenetic markings of the chromatin, changing the cell fate necessitates broad changes to these central cellular features. To properly characterize these changes, and the mechanisms that drive them, computational and genomic approaches are perfectly suited to provide a holistic picture of the reprogramming mechanisms. In particular, the use of bioinformatic analysis has been a major driver in the study of cellular reprogramming, as it relates to both induced pluripotency or direct lineage conversion. This review will summarize many of the bioinformatic studies that have advanced our knowledge of reprogramming and address future directions for these investigations.

Partial cellular reprogramming: A deep dive into an emerging rejuvenation technology

“…Using a single‐cell RNA‐seq and multi‐omic profiling approach, they identified key contributors to reprogramming variability in aged fibroblasts such as inflammatory cytokines (Mahmoudi et al., 2019 ). At the same time, groups have used a bioinformatic approach to mine reprogramming data sets in order to enable identification of shared gene targets and enriched cellular pathways that could be utilized to develop enhanced reprogramming (Kareta, 2016 ; Knyazer et al., 2021 ). In this line, Calico recently performed a screening of reprogramming factors to better characterize reprogramming induced rejuvenation while simultaneously identifying a novel multipotent strategy derived from amphibian regeneration and the MSX1 transcription factor (Roux et al., 2022 ).…”