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Histone Modification Profiling Reveals Differential Signatures Associated With Human Embryonic Stem Cell Self-renewal And Differentiation.

Natarajan V. Bhanu, S. Sidoli, B. Garcia
Published 2016 · Medicine, Biology

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In this study, we trace developmental stages using epigenome changes in human embryonic stem cells (hESCs) treated with drugs modulating either self-renewal or differentiation. Based on microscopy, qPCR and flow cytometry, we classified the treatment outcome as inducing pluripotency (hESC, flurbiprofen and gatifloxacin), mesendoderm (sinomenine), differentiation (cyamarin, digoxin, digitoxin, selegeline and theanine) and lineage-commitment (RA). When we analyzed histone PTMs that imprinted these gene and protein expressions, the above classification was reassorted. Hyperacetylation at H3K4, 9, 14, 18, 56 and 122 as well as H4K5, 8, 12 and 16 emerged as the pluripotency signature of hESCs. Methylations especially of H3 at K9, K20, K27 and K36 characterized differentiation initiation as seen in no-drug control and fluribiprofen. Sinomenine-treated cells clustered close to "differentiation initiators", consistent with flow cytometry where it induced mesendoderm, along with cyamarin and possibly selegnine. Neurectoderm, induced by RA and theanine manifested methylations on H3 shifts to H3.3. By both flow cytometry and histone PTM clustering, it appears that cells treated with gatifloxacin, flurbiprofen, digitoxin and digoxin were not yet lineage-committed or mixed cell types. Taken together, our moderate-throughput histone PTM profiling approach highlighted subtle epigenetic signatures that permitted us to predict divergent lineage progression even in differentiating cells with similar phenotype and gene expression.
This paper references
10.1126/science.166.3905.639
Gene regulation in higher cells.
C. Waddington (1969)
10.1021/PR050385Q
Modular stop and go extraction tips with stacked disks for parallel and multidimensional Peptide fractionation in proteomics.
Y. Ishihama (2006)
10.1007/s00018-010-0475-7
The significance, development and progress of high-throughput combinatorial histone code analysis
Nicolas L Young (2010)
10.4161/cam.4.1.10627
Definitive endoderm derived from human embryonic stem cells highly express the integrin receptors αV and β5
J. Wong (2010)
10.1016/j.stem.2008.05.010
High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells.
Sabrina C. Desbordes (2008)
10.1016/j.cell.2012.08.027
A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development
S. Paige (2012)
10.1038/ng.154
Combinatorial patterns of histone acetylations and methylations in the human genome
Z. Wang (2008)
10.1093/hmg/ddq476
Epigenetic signatures and temporal expression of lineage-specific genes in hESCs during differentiation to hepatocytes in vitro.
H. Kim (2011)
10.1016/j.stem.2010.03.020
Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture.
Y. Zeng (2010)
10.1016/j.stem.2009.04.012
Using small molecules to great effect in stem cell differentiation.
K. Zaret (2009)
10.1038/343657a0
Expression pattern of the mouse T gene and its role in mesoderm formation
D. Wilkinson (1990)
10.1016/j.gde.2012.05.005
New lessons learned from disease modeling with induced pluripotent stem cells.
T. Onder (2012)
10.1038/nbt.1529
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
S. Chambers (2009)
10.1002/jcb.22183
Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.
John T. Butler (2009)
10.1038/nchembio.154
A small molecule that directs differentiation of human ESCs into the pancreatic lineage.
Shuibing Chen (2009)
10.1016/j.stem.2008.10.004
Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds.
Y. Shi (2008)
10.1093/bfgp/elt050
Epigenomics and the concept of degeneracy in biological systems
R. Maleszka (2014)
10.1016/j.stem.2009.04.001
A small molecule primes embryonic stem cells for differentiation.
Shoutian Zhu (2009)
10.1016/J.DEVCEL.2005.10.017
Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells.
E. Meshorer (2006)
10.1038/nbt1418
Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds
Danwei Huangfu (2008)
10.1016/j.stem.2008.07.027
Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states.
K. Hayashi (2008)
10.1634/stemcells.2007-0951
Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells.
J. Kopp (2008)
10.1073/pnas.1309914110
Acetylated histone H3K56 interacts with Oct4 to promote mouse embryonic stem cell pluripotency
Yuliang Tan (2013)
10.3824/stembook.1.42.1
Epigenetic silencing during early lineage commitment
Howard Cedar (2009)
10.1074/mcp.M114.046011
EpiProfile Quantifies Histone Peptides With Modifications by Extracting Retention Time and Intensity in High-resolution Mass Spectra*
Zuo-Fei Yuan (2015)
10.1074/jbc.M114.603761
Dual Roles of Histone H3 Lysine 9 Acetylation in Human Embryonic Stem Cell Pluripotency and Neural Differentiation*
Yunbo Qiao (2014)
Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages.
S. Nishikawa (1998)
10.1073/pnas.0710515105
Mass spectrometry identifies and quantifies 74 unique histone H4 isoforms in differentiating human embryonic stem cells
Doug Phanstiel (2008)
10.1016/j.jprot.2011.12.029
Proteomics in chromatin biology and epigenetics: Elucidation of post-translational modifications of histone proteins by mass spectrometry.
S. Sidoli (2012)
10.1016/j.stem.2011.06.002
Cell fate potential of human pluripotent stem cells is encoded by histone modifications.
Seok-Ho Hong (2011)
10.1016/j.stem.2009.01.014
Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells.
M. Borowiak (2009)
10.1038/ncomms1915
Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation.
Shai Melcer (2012)
10.1038/ng1637
Genome-scale profiling of histone H3.3 replacement patterns
Yoshiko Mito (2005)
10.1038/nchembio.599
A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells.
M. Vedadi (2011)
10.1159/000076701
Human Embryonic Stem Cells Form Embryoid Bodies Containing Visceral Endoderm-Like Derivatives
B. Conley (2004)
10.1586/epr.12.30
Role of mass spectrometry-based proteomics in the study of cellular reprogramming and induced pluripotent stem cells
Marco Benevento (2012)
10.1016/B978-0-12-391940-3.00001-9
Examining histone posttranslational modification patterns by high-resolution mass spectrometry.
Shu Lin (2012)



This paper is referenced by
10.18632/aging.103567
SIRT6 mono-ADP ribosylates KDM2A to locally increase H3K36me2 at DNA damage sites to inhibit transcription and promote repair
S. Rezazadeh (2020)
10.1186/s13287-019-1454-z
Flow-enhanced priming of hESCs through H2B acetylation and chromatin decondensation
Jiawen Wang (2019)
10.1371/journal.pone.0203351
Stability of histone post-translational modifications in samples derived from liver tissue and primary hepatic cells
Philip A Gruppuso (2018)
10.1016/j.stem.2017.09.006
CRISPR/Cas9-Based Engineering of the Epigenome.
Julián Pulecio (2017)
10.1111/iej.12959
Porphyromonas endodontalis reactivates latent Epstein–Barr virus
K Makino (2018)
10.1016/j.gde.2017.07.007
Advances in stem cell proteomics.
Nade Abazova (2017)
10.1002/stem.3068
SMYD2 Drives Mesendodermal Differentiation of Human Embryonic Stem Cells through Mediating the Transcriptional Activation of Key Mesendodermal Genes.
Huajun Bai (2019)
10.1007/s00018-019-03144-y
Understanding histone H3 lysine 36 methylation and its deregulation in disease
J. Li (2019)
10.1007/s40610-017-0050-1
Recent Advances in Understanding Histone Modification Events
Matthew V Holt (2017)
10.1101/185918
A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations
Lev Litichevskiy (2017)
10.1016/j.bmc.2019.02.006
Identification of novel lysine demethylase 5-selective inhibitors by inhibitor-based fragment merging strategy.
Y. Miyake (2019)
10.1038/s41598-019-53681-6
Untargeted histone profiling during naive conversion uncovers conserved modification markers between mouse and human
Laura De Clerck (2019)
10.1016/j.cels.2018.03.012
A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations
Lev Litichevskiy (2018)
Deciphering the Epigenetic Code in Embryonic and Dental Pulp Stem Cells
Dashzeveg Bayarsaihan (2016)
10.1016/j.gep.2018.04.001
Epigenetic modifications in the embryonic and induced pluripotent stem cells.
Rasoul Godini (2018)
10.13005/bpj/1411
Alterations of Genes Involved in Apoptosis and Epigenetic Modulation Associated with Gatifloxacin-Induced Oxidative Stress in Rat Liver
S. Rotimi (2018)
10.3390/genes8050137
Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure
David P. Gavin (2017)
10.1101/687806
Histone methyltransferase MMSET/NSD2 is essential for generation of B1 cell compartment in mice
Marc-Werner Dobenecker (2019)
10.1074/jbc.RA118.004977
Regulation of proline-directed kinases and the trans-histone code H3K9me3/H4K20me3 during human myogenesis
Natarajan V. Bhanu (2019)
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