Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment-Reference-Cited by-同舟云学术

Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment

Published:2021-02-12 Issue:6530 Volume:371 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Trujillo Cleber A.¹^ORCID,Rice Edward S.²^ORCID,Schaefer Nathan K.²^ORCID,Chaim Isaac A.³^ORCID,Wheeler Emily C.³^ORCID,Madrigal Assael A.³,Buchanan Justin⁴^ORCID,Preissl Sebastian⁴^ORCID,Wang Allen⁴,Negraes Priscilla D.¹^ORCID,Szeto Ryan A.¹^ORCID,Herai Roberto H.⁵^ORCID,Huseynov Alik⁶^ORCID,Ferraz Mariana S. A.⁷^ORCID,Borges Fernando S.⁷^ORCID,Kihara Alexandre H.⁷^ORCID,Byrne Ashley⁸,Marin Maximillian²^ORCID,Vollmers Christopher²^ORCID,Brooks Angela N.²^ORCID,Lautz Jonathan D.⁹¹⁰,Semendeferi Katerina¹¹^ORCID,Shapiro Beth¹²¹³^ORCID,Yeo Gene W.⁴^ORCID,Smith Stephen E. P.⁹¹⁰^ORCID,Green Richard E.²^ORCID,Muotri Alysson R.¹^ORCID

Affiliation:

1. Department of Pediatrics and Department of Cellular & Molecular Medicine, School of Medicine, Center for Academic Research and Training in Anthropogeny (CARTA), Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA 92037, USA.

2. Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

3. Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

4. Department of Cellular & Molecular Medicine, Center for Epigenomics, University of California, San Diego, La Jolla, CA 92093, USA.

5. Experimental Multiuser Laboratory (LEM), Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR 80215-901, Brazil.

6. National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.

7. Laboratório de Neurogenética, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP 09606-070, Brazil.

8. Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

9. Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA.

10. Department of Pediatrics and Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195, USA.

11. Department of Anthropology, Center for Academic Research and Training in Anthropogeny (CARTA), Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA 92037, USA.

12. Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

13. Howard Hughes Medical Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

Abstract

Brain organoids with Neanderthal genes The genomes of Neanderthals and modern humans are overall very similar. To understand the impact of genetic variants that are specific to modern humans, Trujillo et al. performed a genome-wide analysis to identify 61 coding variants in protein-coding genes. Identifying the gene encoding the RNA-binding protein NOVA1 as a top candidate for functional analyses, they introduced the archaic gene variant into human pluripotent stem cells and generated brain organoids. These organoids showed alterations in gene expression and splicing as well as morphology and synaptogenesis, suggesting that this method could be used to explore other genetic changes that underlie the phenotypic traits separating our species from extinct relatives. Science , this issue p. eaax2537

Funder

National Science Foundation

National Institutes of Health

Gordon and Betty Moore Foundation

NARSAD

Neanderthal Brain Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference76 articles.

1. The Human Genus