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Status |
Public on Jan 27, 2017 |
Title |
Gender Differences in Global but not Targeted Demethylation in iPSC Reprogramming |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing
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Summary |
Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires AID-mediated downregulation of UHRF1 protein and abolishing demethylation leaves thousands of hypermethylated regions in the iPSCs genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.
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Overall design |
mRNA-seq and BS-seq of different time-points during iPSC reprogramming
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Contributor(s) |
Milagre I, Stubbs TM, King MR, Spindel J, Santos F, Krueger F, Bachman M, Segonds-Pichon A, Balasubramanian S, Andrews SR, Dean W, Reik W |
Citation(s) |
28147265 |
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Submission date |
Jun 12, 2015 |
Last update date |
Feb 15, 2024 |
Contact name |
Felix Krueger |
E-mail(s) |
fkrueger@altoslabs.com
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Organization name |
Altos Labs
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Department |
Bioinformatics
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Street address |
Granta Park
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City |
Cambridge |
ZIP/Postal code |
CB21 6GP |
Country |
United Kingdom |
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Platforms (2) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (203)
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GSM1709593 |
BS_seq_ESC_1 |
GSM1709594 |
BS_seq_ESC_2 |
GSM1709595 |
BS_seq_ESC_3 |
GSM1709596 |
BS_seq_d6_Thy1_positive_1 |
GSM1709597 |
BS_seq_d6_Thy1_positive_2 |
GSM1709598 |
BS_seq_d6_Thy1_positive_3 |
GSM1709599 |
BS_seq_d6_SSEA1_positive_1 |
GSM1709600 |
BS_seq_d6_SSEA1_positive_2 |
GSM1709601 |
BS_seq_d6_SSEA1_positive_3 |
GSM1709602 |
BS_seq_d21 iPSC_Clone1 |
GSM1709605 |
BS_seq_d29 iPSC_Clone1 |
GSM1709608 |
BS_seq_d60 iPSC_Clone1 |
GSM1709611 |
RNA_Seq_MEF_1 |
GSM1709612 |
RNA_Seq_MEF_2 |
GSM1709613 |
RNA_Seq_MEF_3 |
GSM1709614 |
RNA_Seq_ESC_1 |
GSM1709615 |
RNA_Seq_ESC_2 |
GSM1709616 |
RNA_Seq_ESC_3 |
GSM1709617 |
RNA_Seq_d6_Thy1_positive_1 |
GSM1709618 |
RNA_Seq_d6_Thy1_positive_2 |
GSM1709619 |
RNA_Seq_d6_Thy1_positive_3 |
GSM1709620 |
RNA_Seq_d6_SSEA1_positive_1 |
GSM1709621 |
RNA_Seq_d6_SSEA1_positive_2 |
GSM1709622 |
RNA_Seq_d6_SSEA1_positive_3 |
GSM1709623 |
RNA_Seq_d21 iPSC_Clone1 |
GSM1709626 |
RNA_Seq_d29 iPSC_Clone1 |
GSM1709629 |
RNA_Seq_d60 iPSC_Clone1 |
GSM2463121 |
RNA_seq_AIDKO_MEF1 |
GSM2463122 |
RNA_seq_AIDKO_MEF2 |
GSM2463123 |
RNA_seq_d29_AIDKO_iPSC_Clone1 |
GSM2463124 |
RNA_seq_d29_AIDKO_iPSC_Clone2 |
GSM2463125 |
RNA_seq_d60_AIDKO_iPSC_Clone1 |
GSM2463126 |
RNA_seq_d60_AIDKO_iPSC_Clone2 |
GSM2463127 |
RNA_seq_d21_iPSC_Clone2 |
GSM2463128 |
RNA_seq_d21_iPSC_Clone3 |
GSM2463129 |
RNA_seq_d29_iPSC_Clone2 |
GSM2463130 |
RNA_seq_d29_iPSC_Clone3 |
GSM2463131 |
RNA_seq_d60_iPSC_Clone2 |
GSM2463132 |
RNA_seq_d60_iPSC_Clone3 |
GSM2463133 |
BS_seq_AIDKO_MEF1 |
GSM2463134 |
BS_seq_AIDKO_MEF2 |
GSM2463135 |
BS_seq_d29_AIDKO_iPSC_Clone1 |
GSM2463136 |
BS_seq_d29_AIDKO_iPSC_Clone2 |
GSM2463137 |
BS_seq_d60_AIDKO_iPSC_Clone1 |
GSM2463138 |
BS_seq_d60_AIDKO_iPSC_Clone2 |
GSM2463139 |
BS_seq_d21_iPSC_Clone2 |
GSM2463140 |
BS_seq_d21_iPSC_Clone3 |
GSM2463141 |
BS_seq_d29_iPSC_Clone2 |
GSM2463142 |
BS_seq_d29_iPSC_Clone3 |
GSM2463143 |
BS_seq_d60_iPSC_Clone2 |
GSM2463144 |
BS_seq_d60_iPSC_Clone3 |
GSM2463145 |
BS_seq_d29_MALE_iPSC_Clone1 |
GSM2463146 |
BS_seq_d29_MALE_iPSC_Clone2 |
GSM2463147 |
BS_seq_d29_MALE_iPSC_Clone3 |
GSM2463148 |
BS_seq_d60_MALE_iPSC_Clone1 |
GSM2463149 |
BS_seq_d60_MALE_iPSC_Clone2 |
GSM2463150 |
BS_seq_d60_MALE_iPSC_Clone3 |
GSM2463151 |
BS_seq_MALE_MEF_1 |
GSM2463152 |
BS_seq_MALE_MEF_2 |
GSM2463153 |
BS_seq_MALE_MEF_3 |
GSM8078050 |
BS_seq, Y2_d47_SSEA4_rep1 |
GSM8078051 |
BS_seq, Y1_Fib_rep1 |
GSM8078052 |
BS_seq, N3_d29_CD13_rep1 |
GSM8078053 |
BS_seq, O2_d47_SSEA4_rep1 |
GSM8078054 |
BS_seq, N2_d47_SSEA4_rep1 |
GSM8078055 |
BS_seq, Y1_d54_SSEA4_rep1 |
GSM8078056 |
BS_seq, N3_d29_SSEA4_rep1 |
GSM8078057 |
BS_seq, O1_d47_SSEA4_rep1 |
GSM8078058 |
BS_seq, N3_d54_SSEA4_rep1 |
GSM8078059 |
BS_seq, O2_d54_SSEA4_rep1 |
GSM8078060 |
BS_seq, N2_d54_SSEA4_rep1 |
GSM8078061 |
BS_seq, Y2_Fib_rep1 |
GSM8078062 |
BS_seq, O1_d54_SSEA4_rep1 |
GSM8078063 |
BS_seq, Y1_d47_SSEA4_rep1 |
GSM8078064 |
BS_seq, Y2_d54_SSEA4_rep1 |
GSM8078065 |
BS_seq, N3_d47_SSEA4_rep1 |
GSM8078066 |
BS_seq, Y1_d21_CD13_rep1 |
GSM8078067 |
BS_seq, N2_d21_CD13_rep1 |
GSM8078068 |
BS_seq, O1_d11_CD13_rep1 |
GSM8078069 |
BS_seq, N2_d11_CD13_rep1 |
GSM8078070 |
BS_seq, O2_d21_CD13_rep1 |
GSM8078071 |
BS_seq, Y1_d11_SSEA4_rep1 |
GSM8078072 |
BS_seq, O1_d11_SSEA4_rep1 |
GSM8078073 |
BS_seq, O1_Fib_rep1 |
GSM8078074 |
BS_seq, O1_d29_SSEA4_rep1 |
GSM8078075 |
BS_seq, N2_d34_SSEA4_rep1 |
GSM8078076 |
BS_seq, N2_d11_SSEA4_rep1 |
GSM8078077 |
BS_seq, N2_Fib_rep1 |
GSM8078078 |
BS_seq, Y2_d11_SSEA4_rep1 |
GSM8078079 |
BS_seq, O2_d40_SSEA4_rep1 |
GSM8078080 |
BS_seq, Y2_d34_SSEA4_rep1 |
GSM8078081 |
BS_seq, O1_d21_SSEA4_rep1 |
GSM8078082 |
BS_seq, N3_d11_SSEA4_rep1 |
GSM8078083 |
BS_seq, O2_d29_SSEA4_rep1 |
GSM8078084 |
BS_seq, Y2_d40_SSEA4_rep1 |
GSM8078085 |
BS_seq, O1_d40_SSEA4_rep1 |
GSM8078086 |
BS_seq, O2_d34_SSEA4_rep1 |
GSM8078087 |
BS_seq, N3_d40_SSEA4_rep1 |
GSM8078088 |
BS_seq, N2_d29_SSEA4_rep1 |
GSM8078089 |
BS_seq, N2_d21_SSEA4_rep1 |
GSM8078090 |
BS_seq, Y2_d21_SSEA4_rep1 |
GSM8078091 |
BS_seq, N2_d29_CD13_rep1 |
GSM8078092 |
BS_seq, Y2_d21_CD13_rep1 |
GSM8078093 |
BS_seq, O1_d34_SSEA4_rep1 |
GSM8078094 |
BS_seq, O2_Fib_rep1 |
GSM8078095 |
BS_seq, O2_d29_CD13_rep1 |
GSM8078096 |
BS_seq, Y1_d34_SSEA4_rep1 |
GSM8078097 |
BS_seq, Y1_d11_CD13_rep1 |
GSM8078098 |
BS_seq, Y2_d29_CD13_rep1 |
GSM8078099 |
BS_seq, N3_d11_CD13_rep1 |
GSM8078100 |
BS_seq, O2_d11_SSEA4_rep1 |
GSM8078101 |
BS_seq, Y1_d40_SSEA4_rep1 |
GSM8078102 |
BS_seq, Y1_d21_SSEA4_rep1 |
GSM8078103 |
BS_seq, O2_d11_CD13_rep1 |
GSM8078104 |
BS_seq, N2_d40_SSEA4_rep1 |
GSM8078105 |
BS_seq, Y2_d29_SSEA4_rep1 |
GSM8078106 |
BS_seq, O1_d29_CD13_rep1 |
GSM8078107 |
BS_seq, N3_Fib_rep1 |
GSM8078108 |
BS_seq, N3_d21_SSEA4_rep1 |
GSM8078109 |
BS_seq, O2_d21_SSEA4_rep1 |
GSM8078110 |
BS_seq, O2_d21_CD13_rep2 |
GSM8078111 |
BS_seq, N3_d21_CD13_rep1 |
GSM8078112 |
BS_seq, Y2_d11_CD13_rep1 |
GSM8078113 |
BS_seq, N3_d34_SSEA4_rep1 |
GSM8078114 |
BS_seq, O1_d7_CD13_rep1 |
GSM8078115 |
BS_seq, O2_d7_SSEA4_rep1 |
GSM8078116 |
BS_seq, Y1_d7_CD13_rep1 |
GSM8078117 |
BS_seq, O2_d7_CD13_rep1 |
GSM8078118 |
BS_seq, Y1_d7_SSEA4_rep1 |
GSM8078119 |
BS_seq, N3_d7_SSEA4_rep1 |
GSM8078120 |
BS_seq, N2_d7_CD13_rep1 |
GSM8078121 |
BS_seq, O1_d7_SSEA4_rep1 |
GSM8078122 |
BS_seq, N3_d7_CD13_rep1 |
GSM8078123 |
BS_seq, Y2_d9_CD13_rep1 |
GSM8078124 |
BS_seq, Y2_d11_SSEA4_rep2 |
GSM8078125 |
BS_seq, N2_d7_SSEA4_rep1 |
GSM8078126 |
BS_seq, Y2_d11_CD13_rep2 |
GSM8078127 |
BS_seq, Y2_d9_SSEA4_rep1 |
GSM8078128 |
BS_seq, O1_d11_CD13_rep2 |
GSM8078129 |
BS_seq, N2_d9_CD13_rep1 |
GSM8078130 |
BS_seq, Y1_d9_SSEA4_rep1 |
GSM8078131 |
BS_seq, O2_d9_CD13_rep1 |
GSM8078132 |
BS_seq, Y2_d7_SSEA4_rep1 |
GSM8078133 |
BS_seq, N2_d9_SSEA4_rep1 |
GSM8078134 |
BS_seq, N3_d9_CD13_rep1 |
GSM8078135 |
BS_seq, Y1_d11_CD13_rep2 |
GSM8078136 |
BS_seq, Y1_d9_CD13_rep1 |
GSM8078137 |
BS_seq, O1_d9_CD13_rep1 |
GSM8078138 |
BS_seq, O1_d11_SSEA4_rep2 |
GSM8078139 |
BS_seq, Y2_d7_CD13_rep1 |
GSM8078140 |
BS_seq, Y1_d11_SSEA4_rep2 |
GSM8078141 |
BS_seq, O1_d9_SSEA4_rep1 |
GSM8078142 |
BS_seq, N3_d9_SSEA4_rep1 |
GSM8078143 |
BS_seq, O2_d9_SSEA4_rep1 |
GSM8078144 |
BS_seq, O1_d15_CD13_rep1 |
GSM8078145 |
BS_seq, O2_d15_SSEA4_rep1 |
GSM8078146 |
BS_seq, Y1_d15_CD13_rep1 |
GSM8078147 |
BS_seq, O2_d15_CD13_rep1 |
GSM8078148 |
BS_seq, Y1_d15_SSEA4_rep1 |
GSM8078149 |
BS_seq, N3_d15_SSEA4_rep1 |
GSM8078150 |
BS_seq, N2_d15_CD13_rep1 |
GSM8078151 |
BS_seq, O1_d15_SSEA4_rep1 |
GSM8078152 |
BS_seq, N3_d15_CD13_rep1 |
GSM8078153 |
BS_seq, N2_d11_SSEA4_rep2 |
GSM8078154 |
BS_seq, Y2_d13_SSEA4_rep1 |
GSM8078155 |
BS_seq, N3_d13_CD13_rep1 |
GSM8078156 |
BS_seq, Y1_d13_CD13_rep1 |
GSM8078157 |
BS_seq, N2_d15_SSEA4_rep1 |
GSM8078158 |
BS_seq, O2_d11_CD13_rep2 |
GSM8078159 |
BS_seq, N2_d13_CD13_rep1 |
GSM8078160 |
BS_seq, N2_d13_SSEA4_rep1 |
GSM8078161 |
BS_seq, Y2_d13_CD13_rep1 |
GSM8078162 |
BS_seq, O2_d13_CD13_rep1 |
GSM8078163 |
BS_seq, O1_d13_CD13_rep1 |
GSM8078164 |
BS_seq, N2_d11_CD13_rep2 |
GSM8078165 |
BS_seq, Y1_d13_SSEA4_rep1 |
GSM8078166 |
BS_seq, N3_d11_SSEA4_rep2 |
GSM8078167 |
BS_seq, Y2_d15_SSEA4_rep1 |
GSM8078168 |
BS_seq, O2_d13_SSEA4_rep1 |
GSM8078169 |
BS_seq, O1_d13_SSEA4_rep1 |
GSM8078170 |
BS_seq, Y2_d15_CD13_rep1 |
GSM8078171 |
BS_seq, N3_d13_SSEA4_rep1 |
GSM8078172 |
BS_seq, O2_d11_SSEA4_rep2 |
GSM8078173 |
BS_seq, N3_d11_CD13_rep2 |
GSM8078174 |
BS_seq, O1_d11_SSEA4_rep1_deeper_sequencing |
GSM8078175 |
BS_seq, O1_Fib_rep1_deeper_sequencing |
GSM8078176 |
BS_seq, Y2_d11_SSEA4_rep1_deeper_sequencing |
GSM8078177 |
BS_seq, O2_Fib_rep1_deeper_sequencing |
GSM8078178 |
BS_seq, O2_d11_SSEA4_rep1_deeper_sequencing |
GSM8078179 |
BS_seq, O2_d9_SSEA4_rep1_deeper_sequencing |
GSM8078180 |
BS_seq, O2_d54_SSEA4_rep1_deeper_sequencing |
GSM8078181 |
BS_seq, O1_d54_SSEA4_rep1_deeper_sequencing |
GSM8078182 |
BS_seq, Y2_d54_SSEA4_rep1_deeper_sequencing |
GSM8078183 |
BS_seq, O2_d15_SSEA4_rep1_deeper_sequencing |
GSM8078184 |
BS_seq, O1_d15_SSEA4_rep1_deeper_sequencing |
GSM8078185 |
BS_seq, Y2_Fib_rep1_deeper_sequencing |
GSM8078186 |
BS_seq, Y2_d15_SSEA4_rep1_deeper_sequencing |
GSM8078187 |
BS_seq, O2_d7_SSEA4_rep1_deeper_sequencing |
GSM8078188 |
BS_seq, O1_d7_SSEA4_rep1_deeper_sequencing |
GSM8078189 |
BS_seq, Y2_d7_SSEA4_rep1_deeper_sequencing |
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Relations |
BioProject |
PRJNA286869 |
SRA |
SRP059433 |
Supplementary file |
Size |
Download |
File type/resource |
GSE69823_RAW.tar |
7.8 Gb |
(http)(custom) |
TAR (of COV, TXT) |
GSE69823_Reprogramming_iPSC_RNAseq_Wt.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |
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