Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.1038/s41467-018-05071-1 |
Resumo: | Bistable switches are common gene regulatory motifs directing two mutually exclusive cell fates. Theoretical studies suggest that bistable switches are sufficient to encode more than two cell fates without rewiring the circuitry due to the non-equilibrium, heterogeneous cellular environment. However, such a scenario has not been experimentally observed. Here by developing a new, dual single-molecule gene-expression reporting system, we find that for the two mutually repressing transcription factors CI and Cro in the classic bistable bacteriophage λ switch, there exist two new production states, in which neither CI nor Cro is produced, or both CI and Cro are produced. We construct the corresponding potential landscape and map the transition kinetics among the four production states. These findings uncover cell fate potentials beyond the classical picture of bistable switches, and open a new window to explore the genetic and environmental origins of the cell fate decision-making process in gene regulatory networks. |
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Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switchChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)Bistable switches are common gene regulatory motifs directing two mutually exclusive cell fates. Theoretical studies suggest that bistable switches are sufficient to encode more than two cell fates without rewiring the circuitry due to the non-equilibrium, heterogeneous cellular environment. However, such a scenario has not been experimentally observed. Here by developing a new, dual single-molecule gene-expression reporting system, we find that for the two mutually repressing transcription factors CI and Cro in the classic bistable bacteriophage λ switch, there exist two new production states, in which neither CI nor Cro is produced, or both CI and Cro are produced. We construct the corresponding potential landscape and map the transition kinetics among the four production states. These findings uncover cell fate potentials beyond the classical picture of bistable switches, and open a new window to explore the genetic and environmental origins of the cell fate decision-making process in gene regulatory networks.Molecular, Structural and Cellular Microbiology (MOSTMICRO)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNFang, XiaonaLiu, QiongBohrer, ChristopherHensel, ZachHan, WeiWang, JinXiao, Jie2019-04-26T22:14:15Z2018-12-012018-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.1038/s41467-018-05071-1eng2041-1723PURE: 12363866http://www.scopus.com/inward/record.url?scp=85050388148&partnerID=8YFLogxKhttps://doi.org/10.1038/s41467-018-05071-1info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:32:01Zoai:run.unl.pt:10362/67798Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:34:39.904607Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
title |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
spellingShingle |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch Fang, Xiaona Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
title_short |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
title_full |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
title_fullStr |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
title_full_unstemmed |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
title_sort |
Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch |
author |
Fang, Xiaona |
author_facet |
Fang, Xiaona Liu, Qiong Bohrer, Christopher Hensel, Zach Han, Wei Wang, Jin Xiao, Jie |
author_role |
author |
author2 |
Liu, Qiong Bohrer, Christopher Hensel, Zach Han, Wei Wang, Jin Xiao, Jie |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Molecular, Structural and Cellular Microbiology (MOSTMICRO) Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
dc.contributor.author.fl_str_mv |
Fang, Xiaona Liu, Qiong Bohrer, Christopher Hensel, Zach Han, Wei Wang, Jin Xiao, Jie |
dc.subject.por.fl_str_mv |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
topic |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
description |
Bistable switches are common gene regulatory motifs directing two mutually exclusive cell fates. Theoretical studies suggest that bistable switches are sufficient to encode more than two cell fates without rewiring the circuitry due to the non-equilibrium, heterogeneous cellular environment. However, such a scenario has not been experimentally observed. Here by developing a new, dual single-molecule gene-expression reporting system, we find that for the two mutually repressing transcription factors CI and Cro in the classic bistable bacteriophage λ switch, there exist two new production states, in which neither CI nor Cro is produced, or both CI and Cro are produced. We construct the corresponding potential landscape and map the transition kinetics among the four production states. These findings uncover cell fate potentials beyond the classical picture of bistable switches, and open a new window to explore the genetic and environmental origins of the cell fate decision-making process in gene regulatory networks. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-01 2018-12-01T00:00:00Z 2019-04-26T22:14:15Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.1038/s41467-018-05071-1 |
url |
https://doi.org/10.1038/s41467-018-05071-1 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-1723 PURE: 12363866 http://www.scopus.com/inward/record.url?scp=85050388148&partnerID=8YFLogxK https://doi.org/10.1038/s41467-018-05071-1 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137968184623104 |