Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics
During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidl...
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| Veröffentlicht in: | PLoS biology 2018-02, Vol.16 (2), p.e2003127 |
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| creator | Sagner, Andreas Gaber, Zachary B Delile, Julien Kong, Jennifer H Rousso, David L Pearson, Caroline A Weicksel, Steven E Melchionda, Manuela Mousavy Gharavy, S Neda Briscoe, James Novitch, Bennett G |
| description | During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation. |
| doi_str_mv | 10.1371/journal.pbio.2003127 |
| format | Article |
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We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.2003127</identifier><identifier>PMID: 29389974</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - physiology ; Biology and Life Sciences ; Cell cycle ; Cell Cycle - genetics ; Crick, Francis ; Data collection ; Developmental biology ; Differentiation ; Fluorescent Dyes - metabolism ; Funding ; Gene expression ; Gene Expression Regulation - physiology ; Genes, Reporter ; Interneurons - cytology ; Medical research ; Medicine ; Medicine and Health Sciences ; Mice, Transgenic ; Motor Neurons - cytology ; Neural stem cells ; Neural tube ; Neurobiology ; Neurogenesis ; Neurogenesis - genetics ; Neurons ; Neurosciences ; Notch protein ; Olig2 protein ; Oligodendrocyte Transcription Factor 2 - genetics ; Oligodendrocyte Transcription Factor 2 - physiology ; Pattern formation ; Patterning ; Phosphorylation ; Receptors, Notch - metabolism ; Regulatory Sequences, Nucleic Acid ; Repressor Proteins - genetics ; Repressor Proteins - physiology ; Rodents ; Signal Transduction ; Signaling ; Single-Cell Analysis ; Stem cells ; Transcription ; Transcription Factor HES-1 - genetics ; Transcription Factor HES-1 - physiology ; Transcriptome</subject><ispartof>PLoS biology, 2018-02, Vol.16 (2), p.e2003127</ispartof><rights>2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Sagner A, Gaber ZB, Delile J, Kong JH, Rousso DL, Pearson CA, et al. (2018) Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics. PLoS Biol 16(2): e2003127. https://doi.org/10.1371/journal.pbio.2003127</rights><rights>2018 Sagner et al 2018 Sagner et al</rights><rights>2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Sagner A, Gaber ZB, Delile J, Kong JH, Rousso DL, Pearson CA, et al. (2018) Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics. PLoS Biol 16(2): e2003127. https://doi.org/10.1371/journal.pbio.2003127</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-c94d1c6b4b030921c97e2c012ff064dbbc266c3b092784f4e5f3388616c963983</citedby><cites>FETCH-LOGICAL-c592t-c94d1c6b4b030921c97e2c012ff064dbbc266c3b092784f4e5f3388616c963983</cites><orcidid>0000-0002-1020-5240</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811045/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811045/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29389974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bronner, Marianne</contributor><creatorcontrib>Sagner, Andreas</creatorcontrib><creatorcontrib>Gaber, Zachary B</creatorcontrib><creatorcontrib>Delile, Julien</creatorcontrib><creatorcontrib>Kong, Jennifer H</creatorcontrib><creatorcontrib>Rousso, David L</creatorcontrib><creatorcontrib>Pearson, Caroline A</creatorcontrib><creatorcontrib>Weicksel, Steven E</creatorcontrib><creatorcontrib>Melchionda, Manuela</creatorcontrib><creatorcontrib>Mousavy Gharavy, S Neda</creatorcontrib><creatorcontrib>Briscoe, James</creatorcontrib><creatorcontrib>Novitch, Bennett G</creatorcontrib><title>Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - physiology</subject><subject>Biology and Life Sciences</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Crick, Francis</subject><subject>Data collection</subject><subject>Developmental biology</subject><subject>Differentiation</subject><subject>Fluorescent Dyes - metabolism</subject><subject>Funding</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - physiology</subject><subject>Genes, Reporter</subject><subject>Interneurons - cytology</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mice, Transgenic</subject><subject>Motor Neurons - cytology</subject><subject>Neural stem cells</subject><subject>Neural tube</subject><subject>Neurobiology</subject><subject>Neurogenesis</subject><subject>Neurogenesis - genetics</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Notch protein</subject><subject>Olig2 protein</subject><subject>Oligodendrocyte Transcription Factor 2 - genetics</subject><subject>Oligodendrocyte Transcription Factor 2 - physiology</subject><subject>Pattern formation</subject><subject>Patterning</subject><subject>Phosphorylation</subject><subject>Receptors, Notch - metabolism</subject><subject>Regulatory Sequences, Nucleic Acid</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - physiology</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Single-Cell Analysis</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transcription Factor HES-1 - genetics</subject><subject>Transcription Factor HES-1 - 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genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - physiology</topic><topic>Biology and Life Sciences</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Crick, Francis</topic><topic>Data collection</topic><topic>Developmental biology</topic><topic>Differentiation</topic><topic>Fluorescent Dyes - metabolism</topic><topic>Funding</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - physiology</topic><topic>Genes, Reporter</topic><topic>Interneurons - cytology</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mice, Transgenic</topic><topic>Motor Neurons - cytology</topic><topic>Neural stem cells</topic><topic>Neural tube</topic><topic>Neurobiology</topic><topic>Neurogenesis</topic><topic>Neurogenesis - genetics</topic><topic>Neurons</topic><topic>Neurosciences</topic><topic>Notch protein</topic><topic>Olig2 protein</topic><topic>Oligodendrocyte Transcription Factor 2 - genetics</topic><topic>Oligodendrocyte Transcription Factor 2 - physiology</topic><topic>Pattern formation</topic><topic>Patterning</topic><topic>Phosphorylation</topic><topic>Receptors, Notch - metabolism</topic><topic>Regulatory Sequences, Nucleic Acid</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - physiology</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Single-Cell Analysis</topic><topic>Stem cells</topic><topic>Transcription</topic><topic>Transcription Factor HES-1 - genetics</topic><topic>Transcription Factor HES-1 - physiology</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sagner, Andreas</creatorcontrib><creatorcontrib>Gaber, Zachary B</creatorcontrib><creatorcontrib>Delile, Julien</creatorcontrib><creatorcontrib>Kong, Jennifer H</creatorcontrib><creatorcontrib>Rousso, David L</creatorcontrib><creatorcontrib>Pearson, Caroline A</creatorcontrib><creatorcontrib>Weicksel, Steven E</creatorcontrib><creatorcontrib>Melchionda, Manuela</creatorcontrib><creatorcontrib>Mousavy Gharavy, S Neda</creatorcontrib><creatorcontrib>Briscoe, James</creatorcontrib><creatorcontrib>Novitch, Bennett G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29389974</pmid><doi>10.1371/journal.pbio.2003127</doi><orcidid>https://orcid.org/0000-0002-1020-5240</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - physiology Biology and Life Sciences Cell cycle Cell Cycle - genetics Crick, Francis Data collection Developmental biology Differentiation Fluorescent Dyes - metabolism Funding Gene expression Gene Expression Regulation - physiology Genes, Reporter Interneurons - cytology Medical research Medicine Medicine and Health Sciences Mice, Transgenic Motor Neurons - cytology Neural stem cells Neural tube Neurobiology Neurogenesis Neurogenesis - genetics Neurons Neurosciences Notch protein Olig2 protein Oligodendrocyte Transcription Factor 2 - genetics Oligodendrocyte Transcription Factor 2 - physiology Pattern formation Patterning Phosphorylation Receptors, Notch - metabolism Regulatory Sequences, Nucleic Acid Repressor Proteins - genetics Repressor Proteins - physiology Rodents Signal Transduction Signaling Single-Cell Analysis Stem cells Transcription Transcription Factor HES-1 - genetics Transcription Factor HES-1 - physiology Transcriptome |
| title | Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics |
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