The Yin and Yang of Chromatin Dynamics In Stem Cell Fate Selection

Adult organisms rely on tissue stem cells for maintenance and repair. During homeostasis, the concerted action of local niche signals and epigenetic regulators establish stable gene expression patterns to ensure that stem cells are not lost over time. However, stem cells also provide host tissues with a remarkable plasticity to respond to perturbations. How adult stem cells choose and acquire new fates is unknown, but the genome-wide mapping of epigenetic landscapes suggests a critical role for chromatin remodeling in these processes. Here, we explore the emerging role of chromatin modifiers and pioneer transcription factors in adult stem cell fate decisions and plasticity, which ensure that selective lineage choices are only made when environmentally cued.

TrendsAdult stem cells coordinate niche signals and chromatin states to choose appropriate fates. Upon changes in the local niche environment, stem cells remodel chromatin to survive in transitional states, before undergoing fate selection.Epigenetic repressors put a brake on precocious lineage commitment. DNA methylation and Polycomb-silencing complexes cooperate to ensure that stem cells are robustly maintained during homeostasis.Cell identity depends on combinatorial transcription factor complexes on lineage-specific enhancers. Pioneer factors select unique enhancer repertoires by making condensed chromatin accessible for robust gene activation.Epigenetic memory is achieved by coupling pioneer factors with super-enhancers, allowing stem cells to retain their unique identities in different microenvironments.