دورية أكاديمية
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Maturation and circuit integration of transplanted human cortical organoids.

التفاصيل البيبلوغرافية
العنوان: Maturation and circuit integration of transplanted human cortical organoids.
المؤلفون: Revah O; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Gore F; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Department of Bioengineering, Stanford University, Stanford, CA, USA., Kelley KW; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Andersen J; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Sakai N; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA., Chen X; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Li MY; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Birey F; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Yang X; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA., Saw NL; Stanford Behavioral and Functional Neuroscience Laboratory, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA., Baker SW; Department of Comparative Medicine, Stanford University, Stanford, CA, USA., Amin ND; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Kulkarni S; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA., Mudipalli R; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Department of Bioengineering, Stanford University, Stanford, CA, USA., Cui B; Department of Chemistry, Stanford University, Stanford, CA, USA., Nishino S; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA., Grant GA; Department of Neurosurgery, Stanford University, Stanford, CA, USA., Knowles JK; Department of Neurology and Neurological Sciences, Stanford, CA, USA., Shamloo M; Stanford Behavioral and Functional Neuroscience Laboratory, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.; Department of Neurosurgery, Stanford University, Stanford, CA, USA., Huguenard JR; Department of Neurology and Neurological Sciences, Stanford, CA, USA., Deisseroth K; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Department of Bioengineering, Stanford University, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA., Pașca SP; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. spasca@stanford.edu.; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA. spasca@stanford.edu.
المصدر: Nature [Nature] 2022 Oct; Vol. 610 (7931), pp. 319-326. Date of Electronic Publication: 2022 Oct 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Neural Pathways* , Organoids*/cytology , Organoids*/innervation , Organoids*/transplantation, Animals ; Animals, Newborn ; Autistic Disorder ; Humans ; Long QT Syndrome ; Motivation ; Neurons/physiology ; Optogenetics ; Rats ; Reward ; Somatosensory Cortex/cytology ; Somatosensory Cortex/physiology ; Stem Cells/cytology ; Syndactyly
مستخلص: Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease 1-5 . However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.
(© 2022. The Author(s).)
التعليقات: Comment in: Nature. 2022 Oct;610(7932):427-428. doi: 10.1038/d41586-022-03238-x. (PMID: 36224372)
Comment in: Cell. 2022 Dec 22;185(26):4869-4872. doi: 10.1016/j.cell.2022.11.020. (PMID: 36563661)
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معلومات مُعتمدة: T32 MH019938 United States MH NIMH NIH HHS; K99 DA050662 United States DA NIDA NIH HHS; S10 RR026917 United States RR NCRR NIH HHS; R01 MH115012 United States MH NIMH NIH HHS; S10 OD030452 United States OD NIH HHS; K08 NS123544 United States NS NINDS NIH HHS
SCR Disease Name: Timothy syndrome
تواريخ الأحداث: Date Created: 20221012 Date Completed: 20221014 Latest Revision: 20240731
رمز التحديث: 20240731
مُعرف محوري في PubMed: PMC9556304
DOI: 10.1038/s41586-022-05277-w
PMID: 36224417
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-022-05277-w