Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum
Embryonic stem cells (ESCs) are characterized by the pluripotent capacity to generate all embryonic lineages. Here, we show that ESCs can occupy a spectrum of distinct transcriptional and epigenetic states in response to varied extrinsic conditions. This spectrum broadly corresponds to a development...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117302217 |
| _version_ | 1818584035313582080 |
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| author | Jamie A. Hackett Toshihiro Kobayashi Sabine Dietmann M. Azim Surani |
| author_facet | Jamie A. Hackett Toshihiro Kobayashi Sabine Dietmann M. Azim Surani |
| author_sort | Jamie A. Hackett |
| collection | DOAJ |
| description | Embryonic stem cells (ESCs) are characterized by the pluripotent capacity to generate all embryonic lineages. Here, we show that ESCs can occupy a spectrum of distinct transcriptional and epigenetic states in response to varied extrinsic conditions. This spectrum broadly corresponds to a developmental continuum of pluripotency and is coupled with a gradient of increasing global DNA methylation. Each pluripotent state is linked with activation of distinct classes of transposable elements (TEs), which in turn influence ESCs through generating chimeric transcripts. Moreover, varied ESC culture parameters differentially license heterogeneous activation of master lineage regulators, including Sox1, Gata4, or Blimp1, and influence differentiation. Activation of Blimp1 is prevalent in 2i (without LIF) conditions, and marks a dynamic primordial germ cell (PGC)-like sub-state that is directly repressed by Klf4 downstream of LIF/STAT3 signaling. Thus, extrinsic cues establish a spectrum of pluripotent states, in part by modulating sub-populations, as well as directing the transcriptome, epigenome, and TE. |
| first_indexed | 2024-12-16T08:14:46Z |
| format | Article |
| id | doaj.art-c4fa1883084d4d8b8f86cc7e15ce071f |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-16T08:14:46Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-c4fa1883084d4d8b8f86cc7e15ce071f2022-12-21T22:38:16ZengElsevierStem Cell Reports2213-67112017-06-01861645165810.1016/j.stemcr.2017.05.014Activation of Lineage Regulators and Transposable Elements across a Pluripotent SpectrumJamie A. Hackett0Toshihiro Kobayashi1Sabine Dietmann2M. Azim Surani3Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UKWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UKWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UKWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UKEmbryonic stem cells (ESCs) are characterized by the pluripotent capacity to generate all embryonic lineages. Here, we show that ESCs can occupy a spectrum of distinct transcriptional and epigenetic states in response to varied extrinsic conditions. This spectrum broadly corresponds to a developmental continuum of pluripotency and is coupled with a gradient of increasing global DNA methylation. Each pluripotent state is linked with activation of distinct classes of transposable elements (TEs), which in turn influence ESCs through generating chimeric transcripts. Moreover, varied ESC culture parameters differentially license heterogeneous activation of master lineage regulators, including Sox1, Gata4, or Blimp1, and influence differentiation. Activation of Blimp1 is prevalent in 2i (without LIF) conditions, and marks a dynamic primordial germ cell (PGC)-like sub-state that is directly repressed by Klf4 downstream of LIF/STAT3 signaling. Thus, extrinsic cues establish a spectrum of pluripotent states, in part by modulating sub-populations, as well as directing the transcriptome, epigenome, and TE.http://www.sciencedirect.com/science/article/pii/S2213671117302217pluripotencychimeric transcriptsDNA methylationPGCtransposable elementSTAT3embryonic stem cellimprintsKLF4heterogeneity |
| spellingShingle | Jamie A. Hackett Toshihiro Kobayashi Sabine Dietmann M. Azim Surani Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum Stem Cell Reports pluripotency chimeric transcripts DNA methylation PGC transposable element STAT3 embryonic stem cell imprints KLF4 heterogeneity |
| title | Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum |
| title_full | Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum |
| title_fullStr | Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum |
| title_full_unstemmed | Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum |
| title_short | Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum |
| title_sort | activation of lineage regulators and transposable elements across a pluripotent spectrum |
| topic | pluripotency chimeric transcripts DNA methylation PGC transposable element STAT3 embryonic stem cell imprints KLF4 heterogeneity |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117302217 |
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