Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes.
Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells, and their membranes ensheath axons, providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies, where the establishment of repressive epigenetic marks on histone proteins, followed by activation of myelin genes, leads to lineage progression. To assess whether this epigenetic regulation is conserved across species, we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation, and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells, differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks, including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species.
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA. pdouvaras@nyscf.org.
Panagiotis
P
Douvaras
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA. trusielewicz@nyscf.org.
Tomasz
T
Rusielewicz
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. kwihyekim@gmail.com.
Kwi Hye
KH
Kim
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. jefferyhaines@gmail.com.
Jeffery D
JD
Haines
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. patrizia.casaccia@mssm.edu.
Patrizia
P
Casaccia
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA. vfossati@nyscf.org.
Valentina
V
Fossati
D000107:Acetylation; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D051792:Basic Helix-Loop-Helix Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D000071841:PAX6 Transcription Factor; C405708:OLIG2 protein, human
histone modifications; human induced pluripotent stem cells; oligodendrocyte differentiation