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The human brain through the lens of somatic mosaicism

Every cell in the human brain possesses a unique genome that is the product of the accumulation of somatic mutations starting from the first postzygotic cell division and continuing throughout life. Somatic mosaicism in the human brain has been the focus of several recent efforts that took advantage...

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Autor principal: Bizzotto, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213359/
https://www.ncbi.nlm.nih.gov/pubmed/37250426
http://dx.doi.org/10.3389/fnins.2023.1172469
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author Bizzotto, Sara
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description Every cell in the human brain possesses a unique genome that is the product of the accumulation of somatic mutations starting from the first postzygotic cell division and continuing throughout life. Somatic mosaicism in the human brain has been the focus of several recent efforts that took advantage of key technological innovations to start elucidating brain development, aging and disease directly in human tissue. On one side, somatic mutation occurring in progenitor cells has been used as a natural barcoding system to address cell phylogenies of clone formation and cell segregation in the brain lineage. On the other side, analyses of mutation rates and patterns in the genome of brain cells have revealed mechanisms of brain aging and disorder predisposition. In addition to the study of somatic mosaicism in the normal human brain, the contribution of somatic mutation has been investigated in both developmental neuropsychiatric and neurodegenerative disorders. This review starts with a methodological perspective on the study of somatic mosaicism to then cover the most recent findings in brain development and aging, and ends with the role of somatic mutations in brain disease. Thus, this review underlies what we have learned and what is still possible to discover by looking at somatic mosaicism in the brain genome.
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spelling pubmed-102133592023-05-27 The human brain through the lens of somatic mosaicism Bizzotto, Sara Front Neurosci Neuroscience Every cell in the human brain possesses a unique genome that is the product of the accumulation of somatic mutations starting from the first postzygotic cell division and continuing throughout life. Somatic mosaicism in the human brain has been the focus of several recent efforts that took advantage of key technological innovations to start elucidating brain development, aging and disease directly in human tissue. On one side, somatic mutation occurring in progenitor cells has been used as a natural barcoding system to address cell phylogenies of clone formation and cell segregation in the brain lineage. On the other side, analyses of mutation rates and patterns in the genome of brain cells have revealed mechanisms of brain aging and disorder predisposition. In addition to the study of somatic mosaicism in the normal human brain, the contribution of somatic mutation has been investigated in both developmental neuropsychiatric and neurodegenerative disorders. This review starts with a methodological perspective on the study of somatic mosaicism to then cover the most recent findings in brain development and aging, and ends with the role of somatic mutations in brain disease. Thus, this review underlies what we have learned and what is still possible to discover by looking at somatic mosaicism in the brain genome. Frontiers Media S.A. 2023-05-12 /pmc/articles/PMC10213359/ /pubmed/37250426 http://dx.doi.org/10.3389/fnins.2023.1172469 Text en Copyright © 2023 Bizzotto. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Bizzotto, Sara
The human brain through the lens of somatic mosaicism
title The human brain through the lens of somatic mosaicism
title_full The human brain through the lens of somatic mosaicism
title_fullStr The human brain through the lens of somatic mosaicism
title_full_unstemmed The human brain through the lens of somatic mosaicism
title_short The human brain through the lens of somatic mosaicism
title_sort human brain through the lens of somatic mosaicism
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213359/
https://www.ncbi.nlm.nih.gov/pubmed/37250426
http://dx.doi.org/10.3389/fnins.2023.1172469
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