Nomenclature for cellular plasticity: are the terms as plastic as the cells themselves?

Abstract

It is now recognized that cell identity is more fluid, and tissues more plastic, than previously thought. The plasticity of cells is relevant to diverse fields, most notably developmental and stem cell biology, regenerative medicine, and cancer biology. To date, a comprehensive and uniform nomenclature to define distinct cell states and their injury-induced interconversions has been elusive. The first Keystone Symposium devoted exclusively to cellular plasticity in regeneration and tumorigenesis was held on January 2019 in Keystone, Colorado, and featured a workshop on terminology in the cell plasticity field. Definitions for terms such as plasticity, de- and transdifferentiation, reversion, and paligenosis were discussed. Here, we summarize the content and tenor of the symposium and nomenclature-focused workshop with regard to terms in the field. We outline the challenges with current definitions and recommend best practices and approaches to developing an accurate and acceptable nomenclature in the future.

Figure 1. Cell plasticity within an adult tissue: common terms and problematic aspects illustrated

An adapted tissue differentiation “landscape” in an adult tissue with an active stem cell is depicted as envisioned by Waddington with several differentiated cells in grooves at the “bottom” of the landscape implying terminal differentiation. The stem cell has potential to roll down several grooves (“differentiate”) into each of the adult cells. A progenitor cell with more limited differentiation options is also depicted. “PLASTICITY TERMS”—commonly used terms in cell plasticity are illustrated as events on the landscape with canonical definitions in blue. Note: Paligenosis describes the cell biological process of converting a mature cell into a regenerative cell, regardless of tissue or “position” on the landscape, so it is not depicted on the landscape. “QUESTIONS”—illustrates scenarios that may not be covered by current terms or that may highlight how current terms can overlap. Inflammation or injury can either change the grooves (i.e., redefine what stable cell lineages are in the tissue or simply lower the threshold for interconversion among different mature or progenitor cell types). Single‐cell analyses like RNA‐Seq suggest that mature cells may be relatively fluid even in steady state such that differentiated cells are not as fixed in a single groove as has been implied by traditional fixed tissues and histological approaches. Transdifferentiation may occur via a dedifferentiation process.