Metastable Pluripotent States in NOD Mouse Derived ES Cells

Embryonic stem (ES) cells are isolated from the inner cell mass (ICM) of blastocysts, whereas epiblast stem cells (EpiSCs) are derived from the post-implantation epiblast and display a restricted developmental potential. Here we characterize pluripotent states in the non-obese diabetic (NOD) mouse...

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Main Authors: Hanna, Jacob, Markoulaki, Styliani, Mitalipova, Maisam, Cassady, John P., Staerk, Judith, Carey, Bryce W., Lengner, Christopher J., Foreman, Ruth K., Love, Jennifer, Gao, Qing, Kim, Jongpil, Jaenisch, Rudolf, Cheng, Albert Wu
Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program
Format: Article
Language:en_US
Published: Elsevier 2012
Online Access:http://hdl.handle.net/1721.1/73889
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author Hanna, Jacob
Markoulaki, Styliani
Mitalipova, Maisam
Cassady, John P.
Staerk, Judith
Carey, Bryce W.
Lengner, Christopher J.
Foreman, Ruth K.
Love, Jennifer
Gao, Qing
Kim, Jongpil
Jaenisch, Rudolf
Cheng, Albert Wu
author2 Massachusetts Institute of Technology. Computational and Systems Biology Program
author_facet Massachusetts Institute of Technology. Computational and Systems Biology Program
Hanna, Jacob
Markoulaki, Styliani
Mitalipova, Maisam
Cassady, John P.
Staerk, Judith
Carey, Bryce W.
Lengner, Christopher J.
Foreman, Ruth K.
Love, Jennifer
Gao, Qing
Kim, Jongpil
Jaenisch, Rudolf
Cheng, Albert Wu
author_sort Hanna, Jacob
collection MIT
description Embryonic stem (ES) cells are isolated from the inner cell mass (ICM) of blastocysts, whereas epiblast stem cells (EpiSCs) are derived from the post-implantation epiblast and display a restricted developmental potential. Here we characterize pluripotent states in the non-obese diabetic (NOD) mouse strain, which prior to this study was considered “non-permissive” for ES cell derivation. We find that NOD stem cells can be stabilized by providing constitutive expression of Klf4 or c-Myc or small molecules that can replace these factors during in vitro reprogramming. The NOD ES and iPS cells appear “metastable”, as they acquire an alternative EpiSC-like identity after removal of the exogenous factors, while their reintroduction converts the cells back to ICM-like pluripotency. Our findings suggest that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro, the stability of which is regulated by endogenous genetic determinants and can be modified by exogenous factors.
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spelling mit-1721.1/738892022-10-01T10:13:16Z Metastable Pluripotent States in NOD Mouse Derived ES Cells Hanna, Jacob Markoulaki, Styliani Mitalipova, Maisam Cassady, John P. Staerk, Judith Carey, Bryce W. Lengner, Christopher J. Foreman, Ruth K. Love, Jennifer Gao, Qing Kim, Jongpil Jaenisch, Rudolf Cheng, Albert Wu Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Cheng, Albert W. Cassady, John P. Foreman, Ruth K. Jaenisch, Rudolf Carey, Bryce W. Embryonic stem (ES) cells are isolated from the inner cell mass (ICM) of blastocysts, whereas epiblast stem cells (EpiSCs) are derived from the post-implantation epiblast and display a restricted developmental potential. Here we characterize pluripotent states in the non-obese diabetic (NOD) mouse strain, which prior to this study was considered “non-permissive” for ES cell derivation. We find that NOD stem cells can be stabilized by providing constitutive expression of Klf4 or c-Myc or small molecules that can replace these factors during in vitro reprogramming. The NOD ES and iPS cells appear “metastable”, as they acquire an alternative EpiSC-like identity after removal of the exogenous factors, while their reintroduction converts the cells back to ICM-like pluripotency. Our findings suggest that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro, the stability of which is regulated by endogenous genetic determinants and can be modified by exogenous factors. National Institutes of Health (U.S.) (Grant RO1-HDO45022) National Institutes of Health (U.S.) (Grant R37-CA084198) National Institutes of Health (U.S.) (Grant RO1-CA087869) 2012-10-11T18:46:53Z 2012-10-11T18:46:53Z 2009-05 2009-04 Article http://purl.org/eprint/type/JournalArticle 1934-5909 http://hdl.handle.net/1721.1/73889 Hanna, Jacob et al. “Metastable Pluripotent States in NOD-Mouse-Derived ESCs.” Cell Stem Cell 4.6 (2009): 513–524. en_US http://dx.doi.org/10.1016/j.stem.2009.04.015 Cell Stem Cell Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier PMC
spellingShingle Hanna, Jacob
Markoulaki, Styliani
Mitalipova, Maisam
Cassady, John P.
Staerk, Judith
Carey, Bryce W.
Lengner, Christopher J.
Foreman, Ruth K.
Love, Jennifer
Gao, Qing
Kim, Jongpil
Jaenisch, Rudolf
Cheng, Albert Wu
Metastable Pluripotent States in NOD Mouse Derived ES Cells
title Metastable Pluripotent States in NOD Mouse Derived ES Cells
title_full Metastable Pluripotent States in NOD Mouse Derived ES Cells
title_fullStr Metastable Pluripotent States in NOD Mouse Derived ES Cells
title_full_unstemmed Metastable Pluripotent States in NOD Mouse Derived ES Cells
title_short Metastable Pluripotent States in NOD Mouse Derived ES Cells
title_sort metastable pluripotent states in nod mouse derived es cells
url http://hdl.handle.net/1721.1/73889
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