Author
Listed:
- Changuk Chung
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Xiaoxu Yang
(University of California San Diego
Rady Children’s Institute for Genomic Medicine
University of Utah)
- Robert F. Hevner
(Sanford Consortium for Regenerative Medicine
University of California, San Diego)
- Katie Kennedy
(BioSkryb Genomics Inc.)
- Keng Ioi Vong
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Yang Liu
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Arzoo Patel
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Rahul Nedunuri
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Scott T. Barton
(University of California, San Diego)
- Geoffroy Noel
(University of California, San Diego)
- Chelsea Barrows
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Valentina Stanley
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Swapnil Mittal
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
- Martin W. Breuss
(University of Colorado School of Medicine)
- Johannes C. M. Schlachetzki
(University of California San Diego
University of California, San Diego)
- Stephen F. Kingsmore
(Rady Children’s Institute for Genomic Medicine)
- Joseph G. Gleeson
(University of California San Diego
Rady Children’s Institute for Genomic Medicine)
Abstract
Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain1–7. Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior–posterior axis precedes restriction in the dorsal–ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.
Suggested Citation
Changuk Chung & Xiaoxu Yang & Robert F. Hevner & Katie Kennedy & Keng Ioi Vong & Yang Liu & Arzoo Patel & Rahul Nedunuri & Scott T. Barton & Geoffroy Noel & Chelsea Barrows & Valentina Stanley & Swapn, 2024.
"Cell-type-resolved mosaicism reveals clonal dynamics of the human forebrain,"
Nature, Nature, vol. 629(8011), pages 384-392, May.
Handle:
RePEc:nat:nature:v:629:y:2024:i:8011:d:10.1038_s41586-024-07292-5
DOI: 10.1038/s41586-024-07292-5
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:629:y:2024:i:8011:d:10.1038_s41586-024-07292-5. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.