Androgens increase excitatory neurogenic potential in human brain organoids

Iva Kelava (), Ilaria Chiaradia, Laura Pellegrini, Alex T. Kalinka and Madeline A. Lancaster ()
Additional contact information
Iva Kelava: Medical Research Council Laboratory of Molecular Biology
Ilaria Chiaradia: Medical Research Council Laboratory of Molecular Biology
Laura Pellegrini: Medical Research Council Laboratory of Molecular Biology
Alex T. Kalinka: University of Cambridge
Madeline A. Lancaster: Medical Research Council Laboratory of Molecular Biology

Nature, 2022, vol. 602, issue 7895, 112-116

Abstract: Abstract The biological basis of male–female brain differences has been difficult to elucidate in humans. The most notable morphological difference is size, with male individuals having on average a larger brain than female individuals1,2, but a mechanistic understanding of how this difference arises remains unknown. Here we use brain organoids3 to show that although sex chromosomal complement has no observable effect on neurogenesis, sex steroids—namely androgens—lead to increased proliferation of cortical progenitors and an increased neurogenic pool. Transcriptomic analysis and functional studies demonstrate downstream effects on histone deacetylase activity and the mTOR pathway. Finally, we show that androgens specifically increase the neurogenic output of excitatory neuronal progenitors, whereas inhibitory neuronal progenitors are not increased. These findings reveal a role for androgens in regulating the number of excitatory neurons and represent a step towards understanding the origin of sex-related brain differences in humans.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-04330-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:602:y:2022:i:7895:d:10.1038_s41586-021-04330-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-04330-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().