iPS cell models

Neural stem cell culture. Fluorescent light micrograph of groups of neural stem cells (neurospheres) in culture. Neural stem cells are able to differentiate into neurons (nerve cells) or support cells (glial cells). They are a potential source of cells to replace damaged or lost brain cells.

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.

GeneVariantSimons cohortASD diagnosis?Number of donors for whom lines are availableSource cell typeLabs that generated iPSCsReferences
N/ASSCYes2FibroblastsFlora VaccarinoMariani et al.1
N/ASSCNo3FibroblastsFlora VaccarinoMariani et al.1
16p11.2 duplicationSimons SearchlightNo5FibroblastsRicardo Dolmetsch or Lauren WeissDeshpande et al.2
16p11.2 deletionSimons SearchlightYes / No14Fibroblasts, erythroblasts or CD4+ lymphocytesRicardo Dolmetsch or Lauren Weiss or NYSCF or IBXDeshpande et al.2
PPP2R5DE200K (x2), E198K (x3), E197K, E420K (x2), Q211PSimons SearchlightAvailable upon request9PBMCs, FibroblastsNYSCF, Kyle Fink
Corrected PPP2R5D E197Kcor, E198Kcor (x2)Simons SearchlightAvailable upon request3CRISPR correction in three iPSC lines from above NYSCF, Kyle Fink
CSNK2A1R47Q (x2), K198R (x2), D156E, R312W, Y50S, R47G, CNVdelSimons Searchlight9PBMCsIBX

* PBMCs = peripheral blood mononuclear cells

Upcoming iPS cell lines

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.

Ordering Instructions:

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 iPSC@SFARI.org 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.

Aliquots of all iPSC lines are stored at the SFARI biorepository at Infinity BiologiX (IBX). Prices are available here. Quality control data are available for most of the lines upon request.

To order:

1) Register with SFARI Base. Please direct all questions about ordering to collections@sfari.org.
 
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.

Generation of iPS cells from biospecimens donated by Simons Simplex Collection (SSC) participants

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:

1) Register with SFARI Base, SFARI’s clearinghouse for data and biospecimens. To register follow the steps detailed here. Note that this step may require your institution to sign SFARI’s Researcher Distribution Agreement (RDA), which can sometimes take 1-2 months. SFARI Base registration will result in the creation of your SF ID.

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 collections@SFARI.org. 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.

References

  1. Mariani J. et al. Cell 162, 375-90 (2015) PubMed
  2. Deshpande A. et al. Cell Rep.21, 2678-2687 (2017) PubMed
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