In vivo modeling of human neuron dynamics and Down syndrome

Author:

Real Raquel123ORCID,Peter Manuel4ORCID,Trabalza Antonio13,Khan Shabana13ORCID,Smith Mark A.13,Dopp Joana1ORCID,Barnes Samuel J.5ORCID,Momoh Ayiba4ORCID,Strano Alessio4ORCID,Volpi Emanuela6ORCID,Knott Graham7,Livesey Frederick J.48ORCID,De Paola Vincenzo13

Affiliation:

1. Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK.

2. Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciencias Biomedicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.

3. Medical Research Council London Institute of Medical Sciences, London W12 0NN, UK.

4. Gurdon Institute and ARUK Stem Cell Research Centre, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QN, UK.

5. UK Dementia Research Institute, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK.

6. University of Westminster, 115 New Cavendish St., London W1W 6UW, UK.

7. EPFL, Lausanne CH-1015, Switzerland.

8. UCL Great Ormond Street Institute of Child Health, 30 Guilford St., London WC1N 1EH, UK.

Abstract

Development of human brain neurons The earliest stages of human brain development are very difficult to monitor, but using induced pluripotent stem cells (iPSCs) can help to elucidate the process. Real et al. transplanted neural progenitors derived from human iPSCs into the brains of adult mice. They used intravital imaging to visualize how resulting neurons grew and connected. The human cells produced neurons that integrated and developed synaptic networks with oscillatory activity. Dendritic pruning was observed and involved a process of branch retraction, not degeneration. Cells derived from individuals with Down syndrome, upon transplantation into the mouse brain, produced neurons that grew normally but showed reduced dendritic spine turnover and less network activity. Science , this issue p. eaau1810

Funder

Wellcome Trust

Medical Research Council

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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