Epigenetic Signatures and Plasticity of Intestinal and Other Stem Cells

Annu Rev Physiol. 2021 Feb 10;83:405-427. doi: 10.1146/annurev-physiol-021119-034520. Epub 2020 Nov 24.


The cardinal properties of adult tissue stem cells are self-renewal and the ability to generate diverse resident cell types. The daily losses of terminally differentiated intestinal, skin, and blood cells require "professional" stem cells to produce replacements. This occurs by continuous expansion of stem cells and their immediate progeny, followed by coordinated activation of divergent transcriptional programs to generate stable cells with diverse functions. Other tissues turn over slowly, if at all, and vary widely in strategies for facultative stem cell activity or interconversion among mature resident cell types (transdifferentiation). Cell fate potential is programmed in tissue-specific configurations of chromatin, which restrict the complement of available genes and cis-regulatory elements, hence allowing specific cell types to arise. Using as a model the transcriptional and chromatin basis of cell differentiation and dedifferentiation in intestinal crypts, we discuss here how self-renewing and other tissues execute homeostatic and injury-responsive stem cell activity.

Keywords: chromatin basis of cell differentiation; dedifferentiation; differentiation; lineage plasticity; stem cell compartments; stem cell plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Lineage / genetics
  • Cell Lineage / physiology
  • Cell Plasticity / genetics*
  • Cell Plasticity / physiology*
  • Epigenesis, Genetic / genetics*
  • Epigenesis, Genetic / physiology*
  • Humans
  • Intestines / physiology*
  • Stem Cells / physiology*