title: Cell fate potential of human pluripotent stem cells is encoded by histone modifications.
abstract: Human embryonic stem cells (hESCs) expressing pluripotency markers are assumed to possess equipotent developmental potential. However, disparate responses to differentiation stimuli functionally illustrate that hESCs generate a spectrum of differentiated cell types, suggestive of lineage bias. Here, we reveal specific cell surface markers that allow subfractionation of hESCs expressing hallmark markers of pluripotency. By direct de novo isolation of these subsets, we demonstrate that propensities for lineage differentiation are balanced with reduced clonogenic self-renewal. Histone modification marks of gene loci associated with pluripotency versus lineage specificity predicted cell fate potential of these subfractions, thereby supporting the absence of uniform bivalency as a molecular paradigm to describe cell fate determination of pluripotent cells. Our study reveals that cell fate potential is encoded within cells comprising hESC cultures, highlighting them as a means to understand the mechanisms of lineage specification of pluripotent cells.
authors: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
authors: Seok-Ho
authors: SH
authors: Hong
authors: Shravanti
authors: S
authors: Rampalli
authors: Jung Bok
authors: JB
authors: Lee
authors: Jamie
authors: J
authors: McNicol
authors: Tony
authors: T
authors: Collins
authors: Jonathan S
authors: JS
authors: Draper
authors: Mickie
authors: M
authors: Bhatia
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D002999:Clone Cells; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D005732:Gangliosides / Q000378:metabolism; D006410:Hematopoiesis; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005732:Gangliosides; D006657:Histones; C062875:ganglioside A2B5; D019009:Proto-Oncogene Proteins c-kit