TY - JOUR
T1 - Somatic mosaicism reveals clonal distributions of neocortical development
AU - NIMH Brain Somatic Mosaicism Network
AU - Breuss, Martin W.
AU - Yang, Xiaoxu
AU - Schlachetzki, Johannes C.M.
AU - Antaki, Danny
AU - Lana, Addison J.
AU - Xu, Xin
AU - Chung, Changuk
AU - Chai, Guoliang
AU - Stanley, Valentina
AU - Song, Qiong
AU - Newmeyer, Traci F.
AU - Nguyen, An
AU - O’Brien, Sydney
AU - Hoeksema, Marten A.
AU - Cao, Beibei
AU - Nott, Alexi
AU - McEvoy-Venneri, Jennifer
AU - Pasillas, Martina P.
AU - Barton, Scott T.
AU - Copeland, Brett R.
AU - Nahas, Shareef
AU - Van Der Kraan, Lucitia
AU - Ding, Yan
AU - Gleeson, Joseph G.
AU - Breuss, Martin W.
AU - Yang, Xiaoxu
AU - Antaki, Danny
AU - Averbuj, Dan
AU - Courchesne, Eric
AU - Ball, Laurel L.
AU - Roy, Subhojit
AU - Weinberger, Daniel
AU - Jaffe, Andrew
AU - Paquola, Apua
AU - Erwin, Jennifer
AU - Shin, Jooheon
AU - McConnell, Michael
AU - Straub, Richard
AU - Narurkar, Rujuta
AU - Mathern, Gary
AU - Walsh, Christopher A.
AU - Lee, Alice
AU - Huang, August Yue
AU - D’Gama, Alissa
AU - Dias, Caroline
AU - Maury, Eduardo
AU - Ganz, Javier
AU - Lodato, Michael
AU - Miller, Michael
AU - Abyzov, Alexej
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/4/28
Y1 - 2022/4/28
N2 - 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.
AB - 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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U2 - 10.1038/s41586-022-04602-7
DO - 10.1038/s41586-022-04602-7
M3 - Article
C2 - 35444276
AN - SCOPUS:85129779690
SN - 0028-0836
VL - 604
SP - 689
EP - 696
JO - Nature
JF - Nature
IS - 7907
ER -