Single cell analyses of ES cells reveal alternative pluripotent cell states and molecular mechanisms that control self-renewal
Single cell analyses of ES cells reveal alternative pluripotent cell states and molecular mechanisms that control self-renewal
Analyses of gene expression in single mouse embryonic stem cells (mESCs) cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM). In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN) reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP) data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB) suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.
207-220
Papatsenko, Dmitri
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Darr, Henia
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Kulakovskiy, Ivan
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Waghray, Avinash
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Makeev, Vsevolod
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MacArthur, Benjamin
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Lemischka, Ihor
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11 August 2015
Papatsenko, Dmitri
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Darr, Henia
3431f610-cf7e-4759-9a2c-54933e16f861
Kulakovskiy, Ivan
448f339c-d6a3-4f0a-9156-981355ac94e6
Waghray, Avinash
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Makeev, Vsevolod
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MacArthur, Benjamin
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Lemischka, Ihor
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Papatsenko, Dmitri, Darr, Henia, Kulakovskiy, Ivan, Waghray, Avinash, Makeev, Vsevolod, MacArthur, Benjamin and Lemischka, Ihor
(2015)
Single cell analyses of ES cells reveal alternative pluripotent cell states and molecular mechanisms that control self-renewal.
Stem Cell Reports, 5 (2), .
(doi:10.1016/j.stemcr.2015.07.004).
Abstract
Analyses of gene expression in single mouse embryonic stem cells (mESCs) cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM). In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN) reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP) data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB) suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.
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- Author's Original
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Accepted/In Press date: 14 July 2015
Published date: 11 August 2015
Organisations:
Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences
Identifiers
Local EPrints ID: 383058
URI: http://eprints.soton.ac.uk/id/eprint/383058
ISSN: 2213-6711
PURE UUID: b013029e-4983-41a3-8433-0bd9f56b583f
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Date deposited: 04 Nov 2015 14:50
Last modified: 15 Mar 2024 03:07
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Contributors
Author:
Dmitri Papatsenko
Author:
Henia Darr
Author:
Ivan Kulakovskiy
Author:
Avinash Waghray
Author:
Vsevolod Makeev
Author:
Ihor Lemischka
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