Long-term development of human iPSC-derived pyramidal neurons quantified after transplantation into the neonatal mouse cortex

D'Alessio, Rosa; Koukouli, Fani; Blanchard, Stéphane; Catteau, Julie; Raïs, Célia; Lemonnier, Thomas; Féraud, Olivier; Bennaceur-Griscelli, Annelise; Groszer, Matthias; Maskos, Uwe

doi:10.1016/j.ydbio.2020.01.009

Cited by 9 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in the present study we did not detect PV neurons that represent the other main class of inhibitory neocortical cells. This indicates that under our experimental conditions, PV neurons were not derived from NPC, and this is in accordance with the recent results reported by D' Alessio et al 23 . We compared the spinogenesis in human pyramidal neurons which had been previously kept in culture for 40-50 days 1, with spinogenesis of pyramidal neurons derived from transplanted NPC in newborn mice 50 days after transplantation.…”

Section: Discussionsupporting

confidence: 94%

“…3. These data confirm that transplanted NPC can give rise to pyramidal cells at later stages of maturation, as we described previously 23 .…”

Section: Mapping Of Axonal Projections Of Transplanted Neurons and Imsupporting

confidence: 92%

“…In addition, it has been reported that vascularization of transplanted human cerebral organoids reduces cell apoptosis 31 . We have also reported a strong vascularization of transplants from NPC by two-photon imaging 23 . This suggests that vascularization may have a strong protective effect as well.…”

Section: Discussionmentioning

confidence: 61%

“…Bregma was used as a visible landmark to localize the injection site. We used the published coordinates Dorso-Lateral = + 1 mm, Antero-Posterior = − 1 mm, depth = − 1 mm to target the cortex, or depth = − 2 mm to target the ventricle 23 . Two µl of resuspended cells were injected slowly using a Hamilton syringe (Hamilton, 65460) unilaterally.…”

Section: Methodsmentioning

confidence: 99%

“…of the study as well as the illustration of spine remodeling is depicted in Fig. 1a-c. For transplantation, we used immunodeficient NOD/SCID mice to achieve full integration of cells beyond 2 weeks post-transplantation as described previously 20,23 .…”

Section: Dendritic Spine Morphogenesis Under In Vitro and In Vivo Conmentioning

confidence: 99%

See 4 more Smart Citations

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

Vitrac

Pons

Balkota

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Using human induced pluripotent stem cells (ipSc), recent studies have shown that the events underlying autism spectrum disorders (ASD) can occur during neonatal development. We previously analyzed the ipSc-derived pyramidal cortical neurons of a subset of patients with ASD carrying de novo heterozygous mutations in postsynaptic SHANK3 protein, in culture. We reported altered spinogenesis of those neurons. the transplantation of human ipSc-derived neuronal precursors into mouse brain represents a novel option for in vivo analysis of mutations affecting the human brain. in this study, we transplanted the neuronal precursor cells (npc) into the cortex of newborn mice to analyze their integration and maturation at early stages of development and studied axonal projections of transplanted human neurons into adult mouse brain. We then co-transplanted npc from a control individual and from a patient carrying a de novo heterozygous SHANK3 mutation. We observed a reduction in cell soma size of selective neuronal categories and in axonal projections at 30 days post-transplantation. In contrast to previous in vitro studies, we did not observe any alteration in spinogenesis at this early age. The humanized chimeric mouse models offer the means to analyze ASD-associated mutations further and provide the opportunity to visualize phenotypes in vivo. The use of human-derived cellular models to study neurodevelopmental disorders such as autism spectrum disorders (ASD) is an appropriate approach to link causal genetic alterations to molecular mechanisms that may occur in humans during pre-and postnatal brain development. The "SH3 and multiple ankyrin repeat domain 3" (SHANK3) is a member of the SHANK gene family located on chromosome 22 in humans which contains multiple structural domains as we previously demonstrated by homology modeling 1. Mutations in SHANK3 represent some of the best-known genetic causes for ASD and account for the severe intellectual deficiency (ID) and language deficits observed in 1-2% of patients with ASD 2,3. SHANK3 haploinsufficiency also contributes to the clinical symptoms of patients with Phelan-McDermid syndrome which presents a deletion of chromosome 22q13 that includes SHANK3 in the large majority of cases 4,5. SHANK3 is a critical partner of a major signaling complex expressed at postsynaptic densities (PSD) of glutamatergic synapses which involves cytoskeletal networks at both the soma and the neurites of neuronal cells 6. SHANK3 therefore plays a crucial role in synapse formation and dendritic spine maturation. The fundamental role of SHANK3 at such excitatory synapses was initially investigated by using genetically modified mouse models 7-9 , or by overexpressing mutated SHANK3 protein in transfected rat neurons in culture 10. Human induced pluripotent stem cells (iPSC)-derived neurons represent a valuable model for in vitro analysis of SHANK3 deficiencies in humans 11-15. Accordingly, we recently selected four independent patients with heterozygous truncating de novo SHANK3 point mutations wh...

show abstract

Section: Discussionsupporting

confidence: 94%

“…3. These data confirm that transplanted NPC can give rise to pyramidal cells at later stages of maturation, as we described previously 23 .…”

Section: Mapping Of Axonal Projections Of Transplanted Neurons and Imsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Section: Dendritic Spine Morphogenesis Under In Vitro and In Vivo Conmentioning

confidence: 99%

See 3 more Smart Citations

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

Vitrac

Pons

Balkota

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

Humanized Chimeric Mouse Models to Study Human Neural Development and Pathogenesis of Brain Diseases

et al. 2022

Self Cite

View full text Add to dashboard Cite

The development of humanized neural chimeric mouse models consists in grafting human neuronal progenitor cells (NPC) or differentiated neurons derived from induced pluripotent stem cells (iPSC) into the mouse brain at different timepoints. As the main features of cortical networks and their alterations during brain development cannot be reproduced in vitro, these in vivo models have been used to investigate the mechanisms by which reprogrammed human neurons and non-neuronal cells integrate and migrate into the mouse brain at early stages of brain development and display functional activities several months after their grafting. Here, we describe the neonatal grafting technique of human NPC which we use in our laboratory.We also present a new method based on the grafting of human NPC into the brain of mouse embryos, in utero. A third method consists in the stereotaxic grafting of human NPC into selected brain regions of adult mice. The iPSC technology combined with the use of chimeric mouse models offers numerous possibilities to study human neural development within wellcontrolled and defined temporal windows and to model neuropathological disorders.

show abstract

Human-mouse chimeric brain models constructed from iPSC-derived brain cells: Applications and challenges

Zhao,

Liu,

Wang

et al. 2024

Experimental Neurology

View full text Add to dashboard Cite

Long-term development of human iPSC-derived pyramidal neurons quantified after transplantation into the neonatal mouse cortex

Cited by 9 publications

References 27 publications

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

Humanized Chimeric Mouse Models to Study Human Neural Development and Pathogenesis of Brain Diseases

Human-mouse chimeric brain models constructed from iPSC-derived brain cells: Applications and challenges

Contact Info

Product

Resources

About