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Developmental signa...
Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress
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- de Jaime-Soguero, Anchel (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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- Hattemer, Janina (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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- Bufe, Anja (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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- Haas, Alexander (author)
- Department of Molecular Oncology, Section for Cellular Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany
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- van den Berg, Jeroen (author)
- Oncode Institute, Utrecht, Netherlands; Hubrecht Institute, Utrecht, Netherlands; KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, Netherlands; University Medical Center Utrecht, Utrecht, Netherlands
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- van Batenburg, Vincent (author)
- Oncode Institute, Utrecht, Netherlands; Hubrecht Institute, Utrecht, Netherlands; KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, Netherlands; University Medical Center Utrecht, Utrecht, Netherlands
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- Das, Biswajit (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- di Marco, Barbara (author)
- Department of Clinical Neurobiology, University Hospital Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany
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- Androulaki, Stefania (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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- Böhly, Nicolas (author)
- Department of Molecular Oncology, Section for Cellular Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany
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- Landry, Jonathan J. M. (author)
- Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
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- Schoell, Brigitte (author)
- Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
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- Rosa, Viviane S. (author)
- MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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- Villacorta, Laura (author)
- Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
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- Baskan, Yagmur (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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- Trapp, Marleen (author)
- Schaller Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
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- Benes, Vladimir (author)
- Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
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- Chabes, Andrei, Professor (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Shahbazi, Marta (author)
- MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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- Jauch, Anna (author)
- Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
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- Engel, Ulrike (author)
- Nikon Imaging Center at the University of Heidelberg, Bioquant, Heidelberg, Germany
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- Patrizi, Annarita (author)
- Schaller Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
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- Sotillo, Rocio (author)
- Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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- van Oudenaarden, Alexander (author)
- Oncode Institute, Utrecht, Netherlands; Hubrecht Institute, Utrecht, Netherlands; KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, Netherlands; University Medical Center Utrecht, Utrecht, Netherlands
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- Bageritz, Josephine (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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- Alfonso, Julieta (author)
- Department of Clinical Neurobiology, University Hospital Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany
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- Bastians, Holger (author)
- Department of Molecular Oncology, Section for Cellular Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany
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- Acebrón, Sergio P. (author)
- Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- Human development relies on the correct replication, maintenance and segregation of our genetic blueprints. How these processes are monitored across embryonic lineages, and why genomic mosaicism varies during development remain unknown. Using pluripotent stem cells, we identify that several patterning signals—including WNT, BMP, and FGF—converge into the modulation of DNA replication stress and damage during S-phase, which in turn controls chromosome segregation fidelity in mitosis. We show that the WNT and BMP signals protect from excessive origin firing, DNA damage and chromosome missegregation derived from stalled forks in pluripotency. Cell signalling control of chromosome segregation declines during lineage specification into the three germ layers, but re-emerges in neural progenitors. In particular, we find that the neurogenic factor FGF2 induces DNA replication stress-mediated chromosome missegregation during the onset of neurogenesis, which could provide a rationale for the elevated chromosomal mosaicism of the developing brain. Our results highlight roles for morphogens and cellular identity in genome maintenance that contribute to somatic mosaicism during mammalian development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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de Jaime-Soguero ...
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Hattemer, Janina
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Bufe, Anja
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Haas, Alexander
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van den Berg, Je ...
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van Batenburg, V ...
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show more...
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Das, Biswajit
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di Marco, Barbar ...
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Androulaki, Stef ...
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Böhly, Nicolas
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Landry, Jonathan ...
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Schoell, Brigitt ...
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Rosa, Viviane S.
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Villacorta, Laur ...
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Baskan, Yagmur
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Trapp, Marleen
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Benes, Vladimir
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Chabes, Andrei, ...
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Shahbazi, Marta
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Jauch, Anna
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Engel, Ulrike
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Patrizi, Annarit ...
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Sotillo, Rocio
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van Oudenaarden, ...
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Bageritz, Joseph ...
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Alfonso, Julieta
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Bastians, Holger
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Acebrón, Sergio ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature Communica ...
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Umeå University