Modeling the autistic cell: iPSCs recapitulate developmental principles of syndromic and nonsyndromic ASD

Abstract

The opportunity to model autism spectrum disorders (ASD) through generation of patient-derived induced pluripotent stem cells (iPSCs) is currently an emerging topic. Wide-scale research of altered brain circuits in syndromic ASD, including Rett Syndrome, Fragile X Syndrome, Angelman's Syndrome and sporadic Schizophrenia, was made possible through animal models. However, possibly due to species differences, and to the possible contribution of epigenetics in the pathophysiology of these diseases, animal models fail to recapitulate many aspects of ASD. With the advent of iPSCs technology, 3D cultures of patient-derived cells are being used to study complex neuronal phenotypes, including both syndromic and nonsyndromic ASD. Here, we review recent advances in using iPSCs to study various aspects of the ASD neuropathology, with emphasis on the efforts to create in vitro model systems for syndromic and nonsyndromic ASD. We summarize the main cellular activity phenotypes and aberrant genetic interaction networks that were found in iPSC-derived neurons of syndromic and nonsyndromic autistic patients.

Human in vitro models for understanding mechanisms of autism spectrum disorder

“…These mutations include ASD-associated CNVs such as 15q11q13 deletion (Angelman syndrome) [121] and duplication (Dup15q syndrome) [122], 22q11.2 deletion (DiGeorge syndrome) [123,124], 16p11.2 deletion and duplication [125], and 15q13.3 deletion [126], as well as single-gene mutations including SHANK3 [127][128][129][130], CHD8 [131,132], NRXN1 [133][134][135][136][137], NLGN4 [138], EHMT1 (Kleefstra syndrome) [139], PTCHD1-AS [140], UBE3A (Angelman's syndrome) [141], and CACNA1C (Timothy syndrome) [142] (summarized in Table 1). In this review, we will not discuss fragile X syndrome, Rett's syndrome, and tuberous sclerosis-related autism as they have all been extensively reviewed previously [148][149][150][151][152][153][154].…”

Stem cell therapy in autism: recent insights

“…iPSC applications gain much attention also for autism research. 73 Successful reprogramming of peripheral blood-derived mononuclear cells from autistic child into iPSCs has been performed by transgene-free delivery system. 74 Customized iPSCs will help in elucidating the pathogenic mechanisms of ASDs, 75 also for neuronal differentiation and maturation.…”

A Review of the Placenta and Trophoblast Induced Pluripotent Stem Cells in Autism Spectrum Disorder Research

“…Trophoblasts are the precursors of the placenta and play a regulatory role in fetal neural brain development through a highly coordinated sequence of developmental events. Just 8 days after implantation, the trophoblast cells form the syncytiotrophoblast, the outer multinucleated layer, and the cytotrophoblast, the inner mononuclear layer [13]. The syncytiotrophoblast secretes the hormone human chorionic gonadotropin (HCG) which among its various functions is thought to play a role in neurodevelopment.…”