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Molecular landscapes of human hippocampal immature neurons across lifespan.
Zhou, Yi; Su, Yijing; Li, Shiying; Kennedy, Benjamin C; Zhang, Daniel Y; Bond, Allison M; Sun, Yusha; Jacob, Fadi; Lu, Lu; Hu, Peng; Viaene, Angela N; Helbig, Ingo; Kessler, Sudha K; Lucas, Timothy; Salinas, Ryan D; Gu, Xiaosong; Chen, H Isaac; Wu, Hao; Kleinman, Joel E; Hyde, Thomas M; Nauen, David W; Weinberger, Daniel R; Ming, Guo-Li; Song, Hongjun.
Afiliación
  • Zhou Y; Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Su Y; Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Li S; Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kennedy BC; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • Zhang DY; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Bond AM; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Sun Y; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Jacob F; Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Lu L; Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Hu P; Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Viaene AN; Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Helbig I; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kessler SK; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Lucas T; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Salinas RD; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Gu X; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Chen HI; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Wu H; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Kleinman JE; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Hyde TM; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Nauen DW; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Weinberger DR; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • Ming GL; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Song H; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature ; 607(7919): 527-533, 2022 07.
Article en En | MEDLINE | ID: mdl-35794479
Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3-5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6-8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Neurogénesis / Hipocampo / Longevidad / Neuronas Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Humans Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Neurogénesis / Hipocampo / Longevidad / Neuronas Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Humans Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido