Epigenetic reprogramming of stem cells

Christian Orlowski, Tom Karagiannis, Assam El-Osta

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Research


The stem cell is typically defined as a primordial cell type occupying the apex of a developmental hierarchy from which is derived tissue lineages, organ systems or even whole organisms. Unlike di fferentiated cells, stem cells may exhibit broad developmental potency, enabling them to yield these multiple lineages whilst retaining self-renewal capacity for the purposes of continual tissue replenishment. Potency is dependent on the type of stem cell being considered.
Pluripotent embryonic stem cells (ESC) can effectively generate almost all tissues and cell types constituting an entire organism, while adult stem cells (ASC) may only be multipotent and therefore restricted to the maintenance of a specific clade of lineages or a sole lineage. Every cell type is defined by a unique transcriptional programme determined by the organization of the underlying nuclear architecture. Such organization is regulated via the deposition of epigenetic marks that influence both the chromatin structural features and
accessibility of transcription factors that drive specific gene expression profiles. Epigenetic regulation is crucial to thegeneration of the vast phenotypic diversity observed in mammalian systems, \Vhich are comprised of over 200 cell types, especially considering that nearly every cell of the body contains identical genomic DNA composition. It is believed that the combinatorial nature of these epigenetic signatures enables the substantial extension of informational output from the genetic code without actually altering the underlying nucleotide sequence. ESCs are confronted with the formidable task of generating all
of these lineages from a single genome and must undergo large scale reconfiguration of chromatin structure, positioning of epigenetic n1odifications and the types of modifications e1nploycd in order to facilitate the necessary global gene expression changes. This process is tenned epigenetic reprogramming. How these co1nplex processes are regulated is still being elucidated. However, this pheno1nena is not only restricted to embryonic and adult stem cells but is also observed in gametes immediately after fertilization leading up to the generation of the totipotent zygote and the establishment of the earliest discernible cell lineages, the inner cell mass (ICM) and the trophectoderm (TE). Aberrations in epigenetic regulation and reprogrmn1ning
are pertinent to the development of cancer and the challenges encountered \Vith
somatic cell nuclear transfer techniques. Therefore, a better understanding of
epigenetic reprogra1nming within a physiological context will itnprove our ability to harness the cnonnous therapeutic applications of stem cells for tissue regeneration, effective cloning, and cancer treatment.
Original languageEnglish
Title of host publicationEpigenomic Medicine
EditorsTom C. Karagiannis
Place of PublicationKerala, India
PublisherTransworld Research Network
Number of pages20
ISBN (Print)9788178955292
Publication statusPublished - 2011

Cite this