title: Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states.
abstract: Human-induced pluripotent stem cells (hiPSCs) provide an invaluable source for regenerative medicine, but are limited by proficient lineage-specific differentiation. Here we reveal that hiPSCs derived from human fibroblasts (Fibs) versus human cord blood (CB) exhibit indistinguishable pluripotency, but harbour biased propensities for differentiation. Genes associated with germ layer specification were identical in Fib- or CB-derived iPSCs, whereas lineage-specific marks emerge upon differentiation induction of hiPSCs that were correlated to the cell of origin. Differentiation propensities come at the expense of other lineages and cannot be overcome with stimuli for alternative cell fates. Although incomplete DNA methylation and distinct histone modifications of lineage-specific loci correlate to lineage-specific transcriptome priming, transitioning hiPSCs into naive state of pluripotency removes iPSC-memorized transcriptome. Upon re-entry to the primed state, transcriptome memory is restored, indicating a human-specific phenomenon whereby lineage gated developmental potential is not permanently erased, but can be modulated by the pluripotent state.
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Jung Bok
authors.initials: JB
authors.lastname: Lee
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Shapovalova
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Aline
authors.initials: A
authors.lastname: Fiebig-Comyn
authors.affiliation: 1] McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5 [2] Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Mitchell
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Sarah
authors.initials: S
authors.lastname: Laronde
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Yannick D
authors.initials: YD
authors.lastname: Benoit
authors.affiliation: 1] McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, Canada L8N 3Z5 [2] Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005312:Fetal Blood / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D006657:Histones