Histone Deacetylase Inhibitors in Cell Pluripotency, Differentiation, and Reprogramming

Abstract

Histone deacetylase inhibitors (HDACi) are small molecules that have important and pleiotropic effects on cell homeostasis. Under distinct developmental conditions, they can promote either self-renewal or differentiation of embryonic stem cells. In addition, they can promote directed differentiation of embryonic and tissue-specific stem cells along the neuronal, cardiomyocytic, and hepatic lineages. They have been used to facilitate embryo development following somatic cell nuclear transfer and induced pluripotent stem cell derivation by ectopic expression of pluripotency factors. In the latter method, these molecules not only increase effectiveness, but can also render the induction independent of the oncogenes c-Myc and Klf4. Here we review the molecular pathways that are involved in the functions of HDAC inhibitors on stem cell differentiation and reprogramming of somatic cells into pluripotency. Deciphering the mechanisms of HDAC inhibitor actions is very important to enable their exploitation for efficient and simple tissue regeneration therapies.

Reprogrammed Cell?based Therapy for Liver Disease: From Lab to Clinic

“…Furthermore, epigenetic interferences have also been used to improve hepatic differentiation protocols (32). For instance, sodium butyrate, a specific inhibitor of histone deacetylase, is frequently used to differentiate pluripotent stem cells into different cell lineages including hepatocytes in higher concentrations and longer time intervals (37)(38)(39).…”

Direct reprogramming of somatic cells: an update

“…To improve the efficiency of reprogramming, subsequent studies used polycistronic vector containing four factors, chromatin-modifying chemicals, and mRNAs, in combination with activation or inhibition of various signaling pathways involved in the regulation of cell proliferation Feng et al, 2009;Heinrich and Dimmeler, 2012;Kretsovali et al, 2012).…”

“…Similarly, MyoD was used to reprogram immature chondrocytes, smooth muscle cells, and retinal cells into muscle cells (Choi et al, 1990). In the 1990s, some other transcription factors were discovered, particularly globin transcription factor 1 (Gata-1), that can reprogram avian monocyte precursors into erythrocytes, eosinophils, and megakaryocytes (Kulessa et al, 1995).…”

The Epigenetic Regulation of Wound Healing

“…38 Histone acetylation can weaken the histone-DNA interactions, allowing transcription machinery access, and/or can target acetyl-lysine binding proteins to the specific genomic regions. It is typically associated with gene activation, while deacetylation is associated with gene repression.…”

“…43,44 These properties have highlighted the potential importance of HDAC inhibitors as potential anticancer therapies for a variety of diseases, including skin cancer. 38 Polycomb group (PcG) proteins are incorporated into at least two polycomb repressive complexes (PRCs), known as PRC1 and PRC2, both play roles in chromatin compaction and transcriptional silencing. 45 But despite similar functions, they are structurally and biochemically distinct; PRC1 subunits include Bmi1, MEL18, Ring1A/1B, ring finger protein 2 (RNF2), Cbx, and Phi and PRC2 consists of Ezh2 or Ezh1, Suz12, and Eed.…”