NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State
Naive mouse embryonic stem cells (ESCs) can develop multiple fates, but the cellular and molecular processes that enable lineage competence are poorly characterized. Here, we investigated progression from the ESC ground state in defined culture. We utilized downregulation of Rex1::GFPd2 to track the...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-07-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117302400 |
| _version_ | 1818614866264457216 |
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| author | Carla Mulas Tüzer Kalkan Austin Smith |
| author_facet | Carla Mulas Tüzer Kalkan Austin Smith |
| author_sort | Carla Mulas |
| collection | DOAJ |
| description | Naive mouse embryonic stem cells (ESCs) can develop multiple fates, but the cellular and molecular processes that enable lineage competence are poorly characterized. Here, we investigated progression from the ESC ground state in defined culture. We utilized downregulation of Rex1::GFPd2 to track the loss of ESC identity. We found that cells that have newly downregulated this reporter have acquired capacity for germline induction. They can also be efficiently specified for different somatic lineages, responding more rapidly than naive cells to inductive cues. Inhibition of autocrine NODAL signaling did not alter kinetics of exit from the ESC state but compromised both germline and somatic lineage specification. Transient inhibition prior to loss of ESC identity was sufficient for this effect. Genetic ablation of Nodal reduced viability during early differentiation, consistent with defective lineage specification. These results suggest that NODAL promotes acquisition of multi-lineage competence in cells departing naive pluripotency. |
| first_indexed | 2024-12-16T16:24:49Z |
| format | Article |
| id | doaj.art-f709d1fb088f42439e6122f321d4fff3 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-16T16:24:49Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-f709d1fb088f42439e6122f321d4fff32022-12-21T22:24:47ZengElsevierStem Cell Reports2213-67112017-07-0191779110.1016/j.stemcr.2017.05.033NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground StateCarla Mulas0Tüzer Kalkan1Austin Smith2Wellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKWellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKWellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UKNaive mouse embryonic stem cells (ESCs) can develop multiple fates, but the cellular and molecular processes that enable lineage competence are poorly characterized. Here, we investigated progression from the ESC ground state in defined culture. We utilized downregulation of Rex1::GFPd2 to track the loss of ESC identity. We found that cells that have newly downregulated this reporter have acquired capacity for germline induction. They can also be efficiently specified for different somatic lineages, responding more rapidly than naive cells to inductive cues. Inhibition of autocrine NODAL signaling did not alter kinetics of exit from the ESC state but compromised both germline and somatic lineage specification. Transient inhibition prior to loss of ESC identity was sufficient for this effect. Genetic ablation of Nodal reduced viability during early differentiation, consistent with defective lineage specification. These results suggest that NODAL promotes acquisition of multi-lineage competence in cells departing naive pluripotency.http://www.sciencedirect.com/science/article/pii/S2213671117302400pluripotencyESCsdifferentiationformative pluripotency |
| spellingShingle | Carla Mulas Tüzer Kalkan Austin Smith NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State Stem Cell Reports pluripotency ESCs differentiation formative pluripotency |
| title | NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State |
| title_full | NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State |
| title_fullStr | NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State |
| title_full_unstemmed | NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State |
| title_short | NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State |
| title_sort | nodal secures pluripotency upon embryonic stem cell progression from the ground state |
| topic | pluripotency ESCs differentiation formative pluripotency |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117302400 |
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