Neural precursors, neurons and glial cells, as well as brain organoids, derived from human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have become valuable models in autism spectrum disorder (ASD) research, complementing research studies in animal models. All iPSC lines created from individuals who participated in the Simons Simplex Collection (SSC) and Simons Searchlight are available for distribution to approved researchers as part of the SFARI resources that can be requested through SFARI Base.
We believe the iPSCs from individuals in the Simons collections are especially valuable because many participants received detailed clinical and genetic characterization. For individuals with deletions or duplications of 16p11.2 who participated in Simons VIP Phase I (now part of Simons Searchlight) in particular, a large variety of data (neuropsychological, neuroimaging, genetic) is available. A summary of the data available across individuals in Simons Searchlight can be found here, and the data can be requested through SFARI Base.
iPSC lines that are currently available to order through SFARI Base are summarized in Table 1. This table will be updated as new iPSC lines become available.
Table 1. Available iPSC lines. This table summarizes available iPSC lines by genetic finding (genetic and variant), Simons cohort and ASD diagnosis.
|Gene||Variant||Simons cohort||ASD diagnosis?||Number of donors for whom lines are available||Source cell type||Labs that generated iPSCs||References|
|N/A||SSC||Yes||2||Fibroblasts||Flora Vaccarino||Mariani et al.1|
|N/A||SSC||No||3||Fibroblasts||Flora Vaccarino||Mariani et al.1|
|16p11.2 duplication||Simons Searchlight||No||5||Fibroblasts||Ricardo Dolmetsch or Lauren Weiss||Deshpande et al.2|
|16p11.2 deletion||Simons Searchlight||Yes / No||14||Fibroblasts, erythroblasts or CD4+ lymphocytes||Ricardo Dolmetsch or Lauren Weiss or NYSCF or IBX||Deshpande et al.2|
|ADNP||E720X S763PfsX9 D832KfsX80 K274NfsX31||Simons Searchlight||Available upon request||4||PBMCs||NYSCF|
|CSNK2A1||R47Q (x2), K198R (x2), D156E, R312W, Y50S, R47G, CNVdel||Simons Searchlight||Available upon request||9||PBMCs||IBX|
|DYRK1A||Y219X, W345X, K406fs, C235X, R117X||Simons Searchlight||Available upon request||5||PBMCs||NYSCF|
|GRIN2B||E236X, R696H, G820A (x2), V620M, I751T G611V S555I||Simons Searchlight||Available upon request||8||PBMCs||NYSCF|
|PPP2R5D||E200K (x2), E198K (x3), E197K, E420K (x2), Q211P||Simons Searchlight||Available upon request||9||PBMCs, Fibroblasts||NYSCF, Kyle Fink|
|Corrected PPP2R5D||E197Kcor, E198Kcor (x2)||Simons Searchlight||Available upon request||3||CRISPR correction of three iPSC lines from above||NYSCF, Kyle Fink|
|SCN2A||IVS3+2T>C IVS5+1G>T IVS23+1G>A A263V C959X E1155Afs*2||Simons Searchlight||Available upon request||6||PBMCs||NYSCF|
|SETBP1||E858K R625X H523LfsX32||Simons Searchlight||Available upon request||3||PBMCs||NYSCF|
|SYNGAP1||R1240X K114SfsX20||Simons Searchlight||Available upon request||2||PBMCs||NYSCF|
* PBMCs = peripheral blood mononuclear cells
SFARI is collaborating with the Nancy Lurie Marks Family Foundation (NLMFF) to create iPSCs from ~100 Simons Searchlight participants at the New York Stem Cell Foundation (NYSCF) within the next year. We expect the first 43 iPSC lines resulting from this collaboration to become available May-June 2021 and the second batch of 57 iPSC lines in the fall of 2021.
See Table 2 for a preview of these upcoming iPSC lines here.
If you are interested in ordering iPSC lines listed in Table 1 and require more technical information (e.g., source cell type, reprogramming method or number of available clones), you can email [email protected] with the subject line “SFARI collection iPSCs.” To submit an order for iPSC lines or to request phenotypic or genetic data linked to individual iPSC lines, please follow the ordering instructions below.
2) Review the Researcher Distribution Agreement and sign the joinder agreement.
3) Upload an institutional review board approval or exemption letter for your project in SFARI Base.
4) Submit your request for iPSCs, data or both.
Some individuals who participated in the SSC had the opportunity to donate blood for the generation of immortal cell lines, including iPS cells. Those blood samples are currently stored as cryopreserved lymphocytes (CPLs) in the SFARI biorepository at Infinity BiologiX (IBX). The samples present a non-renewable resource, and therefore SFARI does not provide them to investigators for the creation of iPS cells.
However, we welcome inquiries to use this resource to create iPS cells through the stem cell lab at IBX. Resulting iPSCs would become part of the SFARI biospecimens collection stored at IBX and would be available for request by any qualified researcher.
Researchers can find SSC participants with variants of interest by using the Genotypes and Phenotypes in Families (GPF) tool. In order to get access to GPF, please follow these steps:
If you are already registered in SFARI Base and have an SF ID, go to step 2.
2) Register with GPF using your first and last name, email and SF ID. An automatic email will be sent to you immediately with instructions to create a password.
3) Log into GPF using your email and password.
It is important to note that not every individual who participated in the SSC donated blood or consented to the creation of iPS cells. The GPF tool lists variants identified in the SSC irrespective of blood sample availability or consent status. If you are interested in creating iPS cells from an individual with a specific variant represented in the GPF viewer, please email [email protected]. Our staff can help you determine if the individual you are interested in creating iPS cells for is appropriately consented and if a CPL sample is available.
Note – GPF also houses data from other SFARI projects, namely Simons Searchlight and SPARK; the type of inquiry to create iPS cells described here is specific to samples from the SSC. A list of iPS cells created from participants in Simons Searchlight can be found in Tables 1 and 2 above.
Depending on the particular circumstances of any request—such as the number of iPS cell lines an investigator may want to create, whether the investigator has funding to work with the lines once established, and SFARI’s overall assessment of the demand for those lines from other researchers in the community, SFARI may cover the cost of creating all or some of such cells.