Chromatin Regulation of Tissue Regeneration and Stem Cell Function

Grants and Contracts Details

Description

EDGE CMT: Uncovering Genomic-Epigenomic Interactions Underlying Planarian Stem Cell Function and Whole-worm Regeneration Planarians are free-living flatworms best known for their extraordinary regenerative abilities: many species have the capacity to repattern and reproportion an entirely new worm from almost any piece of amputated tissue. This incredible regenerative potential is dependent on a large, heterogeneous pool of multi- and pluripotent stem cells, which are also required during homeostasis to preserve the integrity and function of mature tissues. As a result, planarians provide a unique, adult, developmental context for studying the maintenance of cellular plasticity and the regulated differentiation of stem cells into multiple lineages – processes that are also essential for successful embryogenesis in any organism. In addition to this impressive and distinctive trait, planarians also bear several features that are morphologically and functionally analogous to those of other animals, including humans. For example, the planarian epidermis comprises a monostratified, mucociliary epithelium that is highly similar to that of the lungs or oviducts. Planarians also possess primitive nephron units, or protonephridia, which share structural, functional, and transcriptional identity with their counterparts in human kidneys. In short, planarians are a powerful, tractable, in vivo animal model for studying many fundamental cellular structures, functions, and processes. The remarkable biology of planarians has been the subject of fascination for centuries, yet the exact molecular mechanisms that confer their distinctive features are still unclear. This knowledge gap is largely due to two key issues: 1) the complexity of these traits and 2) a lack of well-developed molecular and biochemical tools that are tractable in planarian species. However, in my postdoctoral work I pioneered the use of powerful genomic tools to identify the in vivo, functional targets of two essential chromatin-modifying enzymes in planarian stem cells and differentiated tissues (Duncan et al, Cell Reports, 2015). I also recently published the characterization of a newly documented species of highly regenerative planarians, Girardia guanajuatiensis, that display intriguing species-specific differences in stem cell function, epidermal patterning, and regeneration (Duncan et al, biorxiv, 2020). As a principal investigator, I will continue to advance the use of cutting-edge genomic and tools in multiple planarian species in order to identify epigenetic features and mechanisms that govern their unique biology. A major goal in my laboratory is to understand how planarian cells orchestrate the many dynamic changes required for these animals to maintain their two most notable traits — whole animal regeneration and immortal homeostasis — using a single, static genome. We hypothesize that differences in genome accessibility, between cell types and species, play a critical role in regulating the expression of genes required for the maintenance of these distinctive features. 1
StatusFinished
Effective start/end date9/1/216/30/24

Funding

  • National Institute of General Medical Sciences: $1,146,466.00

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