Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos

Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of...

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Main Authors: Lorthongpanich, Chanchao, Cheow, Lih Feng, Balu, Sathish, Quake, Stephen R., Knowles, Barbara B., Burkholder, William F., Solter, Davor, Messerschmidt, Daniel M.
Format: Journal Article
Language:English
Published: 2014
Subjects:
Online Access:https://hdl.handle.net/10356/79976
http://hdl.handle.net/10220/19858
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author Lorthongpanich, Chanchao
Cheow, Lih Feng
Balu, Sathish
Quake, Stephen R.
Knowles, Barbara B.
Burkholder, William F.
Solter, Davor
Messerschmidt, Daniel M.
author_facet Lorthongpanich, Chanchao
Cheow, Lih Feng
Balu, Sathish
Quake, Stephen R.
Knowles, Barbara B.
Burkholder, William F.
Solter, Davor
Messerschmidt, Daniel M.
author_sort Lorthongpanich, Chanchao
collection NTU
description Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of the experimental inaccessibility of early-stage embryos. Here, we introduce a methodologic advance, probing single cells for various DNA-methylation errors at multiple loci, to reveal failed maintenance of epigenetic mark results in chimeric mice, which display unpredictable phenotypes leading to developmental arrest. Yet we show that mouse pronuclear transfer can be used to ameliorate such reprogramming defects. This study not only details the epigenetic reprogramming dynamics in early mammalian embryos but also suggests diagnostic and potential future therapeutic applications.
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spelling ntu-10356/799762020-11-01T05:14:16Z Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos Lorthongpanich, Chanchao Cheow, Lih Feng Balu, Sathish Quake, Stephen R. Knowles, Barbara B. Burkholder, William F. Solter, Davor Messerschmidt, Daniel M. DRNTU::Science::Medicine Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of the experimental inaccessibility of early-stage embryos. Here, we introduce a methodologic advance, probing single cells for various DNA-methylation errors at multiple loci, to reveal failed maintenance of epigenetic mark results in chimeric mice, which display unpredictable phenotypes leading to developmental arrest. Yet we show that mouse pronuclear transfer can be used to ameliorate such reprogramming defects. This study not only details the epigenetic reprogramming dynamics in early mammalian embryos but also suggests diagnostic and potential future therapeutic applications. Accepted version 2014-06-24T05:02:09Z 2019-12-06T13:37:59Z 2014-06-24T05:02:09Z 2019-12-06T13:37:59Z 2013 2013 Journal Article Lorthongpanich, C., Cheow, L. F., Balu, S., Quake, S. R., Knowles, B. B., Burkholder, W. F., et al. (2013). Single-Cell DNA-Methylation Analysis Reveals Epigenetic Chimerism in Preimplantation Embryos. Science, 341(6150), 1110-1112. https://hdl.handle.net/10356/79976 http://hdl.handle.net/10220/19858 10.1126/science.1240617 en Science © 2013 American Association for the Advancement of Science. This is the author created version of a work that has been peer reviewed and accepted for publication by Science, American Association for the Advancement of Science. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1126/science.1240617]. image/jpeg image/jpeg image/jpeg application/pdf application/pdf
spellingShingle DRNTU::Science::Medicine
Lorthongpanich, Chanchao
Cheow, Lih Feng
Balu, Sathish
Quake, Stephen R.
Knowles, Barbara B.
Burkholder, William F.
Solter, Davor
Messerschmidt, Daniel M.
Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
title Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
title_full Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
title_fullStr Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
title_full_unstemmed Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
title_short Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
title_sort single cell dna methylation analysis reveals epigenetic chimerism in preimplantation embryos
topic DRNTU::Science::Medicine
url https://hdl.handle.net/10356/79976
http://hdl.handle.net/10220/19858
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