Epigenetic control of adult stem cell function

Abstract

Mammalian embryonic development is a tightly regulated process that, from a single zygote, produces a large number of cell types with hugely divergent functions. Distinct cellular differentiation programmes are facilitated by tight transcriptional and epigenetic regulation. However, the contribution of epigenetic regulation to tissue homeostasis after the completion of development is less well understood. In this Review, we explore the effects of epigenetic dysregulation on adult stem cell function. We conclude that, depending on the tissue type and the epigenetic regulator affected, the consequences range from negligible to stem cell malfunction and disruption of tissue homeostasis, which may predispose to diseases such as cancer.

Circadian clocks: from stem cells to tissue homeostasis and regeneration

“…This type of stem cells is now known to be present in several organs, such as the bone marrow (hematopoietic stem cells), the intestine (intestinal stem cells), the skin (epidermal stem cells), the heart (cardiac stem cells), and many more organs 10. These cells provide a pool for cell renewal, thereby ensuring tissue homeostasis, but can also be activated specifically upon damage.…”

EMT, CSCs, and drug resistance: the mechanistic link and clinical implications

“…This concept is based on the notion that various phenotypically distinct cancer cells residing within the same tumour mass are organized in a hierarchy, resembling the stem-cell hierarchy of the corresponding non-neoplastic tissue. Indeed, the functional parallels between CSCs and non-neoplastic stem cells are considered to be extensive, including the unique ability to entirely regenerate complex neoplastic and non-neoplastic tissues, respectively, under appropriate conditions 14 . Accordingly, in tumours, the epigenetically defined state of CSCs should, in principle, enable the tumour cells to self-renew in order to generate new CSCs, and to spawn progeny that differentiate into less-tumorigenic and non-self-renewing offspring — that is, the non-CSCs that are thought, in most cases, to form the bulk of the tumour.…”

Epigenetic dysregulation in hematological malignancies

“…New technologies are also uncovering abnormal nuclear topology and chromatin structure in cancer [2]. Recurrent Next-generation sequencing technologies have revealed mutations in a variety of epigenetic regulator genes in cancer [1], and the involvement of epigenetic dysregulation in the development of cancer is now well understood.…”

“…The role of epigenetic gene regulation has been extensively analyzed in hematopoiesis, particularly in hematopoietic stem cells (HSCs) [2]. Analyses of mice deficient for epigenetic regulator genes have shown that epigenetic dysregulation is indeed closely associated with hematological malignancies [3].…”