Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals
| Autor: | Maria Andreina Mendez, Roland Nagy, David Skuse, Eva P. Valencia-Alarcón, Jamie Horder, Irene Lee, Frances Flinter, Grainne M. McAlonan, Simon Baron-Cohen, Declan G. Murphy, Kamila M. Jozwik, Jason S. Carroll, Daniel H. Geschwind, Lucia Dutan, Paulina Nowosiad, Dwaipayan Adhya, Jack Price, Vivek Swarup, Carole Shum, Eva Loth, Deepak Srivastava |
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| Přispěvatelé: | Adhya, Deep [0000-0002-8612-3508], Jozwik, Kamila [0000-0002-0925-7780], Carroll, Jason [0000-0003-3643-0080], Baron-Cohen, Simon [0000-0001-9217-2544], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cortical differentiation Cell type Autism Spectrum Disorder Autism Neurogenesis Neural precursors Neurodevelopment Induced Pluripotent Stem Cells Cell fate determination Biology 03 medical and health sciences 0302 clinical medicine Pregnancy mental disorders medicine Humans Neural progenitor cells Autistic Disorder Induced pluripotent stem cell Biological Psychiatry 030304 developmental biology Progenitor Neurons 0303 health sciences Midbrain differentiation Functional genomics Cell Differentiation medicine.disease Prenatal development Neural stem cell Archival Report 030104 developmental biology Forebrain Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Adhya, D, Swarup, V, Nagy, R, Dutan Polit, L, Shum, C, Valencia-Alarcón, E, Jozwik, K, Mendez Hernandez, M, Horder, J, Loth, E, Nowosiad, P, Lee, I, Skuse, D, Flinter, F, Murphy, D, McAlonan, G, Geschwind, D H, Price, J, Carroll, J, Srivastava, D & Baron-Cohen, S 2020, ' Atypical neurogenesis in induced pluripotent stem cell (iPSC) from autistic individuals ', Biological psychiatry . https://doi.org/10.1016/j.biopsych.2020.06.014 Biological Psychiatry |
| DOI: | 10.1016/j.biopsych.2020.06.014 |
| Popis: | BackgroundAutism is a heterogenous collection of disorders with a complex molecular underpinning. Evidence from post-mortem brain studies using adult brains have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from autistic individuals with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism.MethodsIPSCs were generated from 9 unrelated autistic individuals without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing, control, individuals. IPSCs were differentiated towards either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterise iPSCs at different stage of differentiation.ResultsA subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to post-mortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated towards a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors, and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs.ConclusionsTaken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages. |
| Databáze: | OpenAIRE |
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