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Somatic mosaicism reveals clonal distributions of neocortical development.
Breuss, Martin W; Yang, Xiaoxu; Schlachetzki, Johannes C M; Antaki, Danny; Lana, Addison J; Xu, Xin; Chung, Changuk; Chai, Guoliang; Stanley, Valentina; Song, Qiong; Newmeyer, Traci F; Nguyen, An; O'Brien, Sydney; Hoeksema, Marten A; Cao, Beibei; Nott, Alexi; McEvoy-Venneri, Jennifer; Pasillas, Martina P; Barton, Scott T; Copeland, Brett R; Nahas, Shareef; Van Der Kraan, Lucitia; Ding, Yan; Glass, Christopher K; Gleeson, Joseph G.
Afiliación
  • Breuss MW; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Yang X; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Schlachetzki JCM; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine, Aurora, CO, USA.
  • Antaki D; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Lana AJ; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Xu X; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chung C; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Chai G; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Stanley V; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Song Q; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Newmeyer TF; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Nguyen A; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • O'Brien S; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Hoeksema MA; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Cao B; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Nott A; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • McEvoy-Venneri J; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Pasillas MP; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Barton ST; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Copeland BR; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Nahas S; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Van Der Kraan L; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Ding Y; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Glass CK; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Gleeson JG; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Nature ; 604(7907): 689-696, 2022 04.
Article en En | MEDLINE | ID: mdl-35444276
ABSTRACT
The structure of the human neocortex underlies species-specific traits and reflects intricate developmental programs. Here we sought to reconstruct processes that occur during early development by sampling adult human tissues. We analysed neocortical clones in a post-mortem human brain through a comprehensive assessment of brain somatic mosaicism, acting as neutral lineage recorders1,2. We combined the sampling of 25 distinct anatomic locations with deep whole-genome sequencing in a neurotypical deceased individual and confirmed results with 5 samples collected from each of three additional donors. We identified 259 bona fide mosaic variants from the index case, then deconvolved distinct geographical, cell-type and clade organizations across the brain and other organs. We found that clones derived after the accumulation of 90-200 progenitors in the cerebral cortex tended to respect the midline axis, well before the anterior-posterior or ventral-dorsal axes, representing a secondary hierarchy following the overall patterning of forebrain and hindbrain domains. Clones across neocortically derived cells were consistent with a dual origin from both dorsal and ventral cellular populations, similar to rodents, whereas the microglia lineage appeared distinct from other resident brain cells. Our data provide a comprehensive analysis of brain somatic mosaicism across the neocortex and demonstrate cellular origins and progenitor distribution patterns within the human brain.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Clonales / Neocórtex / Mosaicismo Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Clonales / Neocórtex / Mosaicismo Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article