Neuronal precursors and neurons derived from human induced pluripotent stem cells (iPSCs) have become a valuable model in autism research, complementing research studies in animal models. All iPSC lines created from individuals who participated in the Simons Simplex Collection (SSC) and Simons Variation in Individuals Project (Simons VIP) are available for distribution to approved researchers as part of the ‘SFARI resources.’
We believe the iPSCs from individuals in the Simons collections are especially valuable because all participants were subject to a detailed clinical and genetic characterization, and their phenotypic and genetic data are available to all approved researchers studying autism spectrum disorders.
Currently, iPSC lines for 5 SSC and 14 Simons VIP participants are available. The cause of autism in the 5 SSC participants was undefined (idiopathic)1 (Table 1) at the time the lines were generated. For the Simons VIP, iPSC lines were created for individuals carrying either the copy number duplication or deletion of the chromosomal region 16p11.2 (Table 2). We will update this list as more lines become available.
Because no generally accepted standard for the creation of iPSCs exists, the Simons Foundation Autism Research Initiative (SFARI) has collaborated with RUCDR Infinite Biologics (formerly Rutgers University Cell and DNA Repository) and the New York Stem Cell Foundation (NYSCF) to better understand the sources of variability among iPSC lines generated from varying source cells with different re-programming methods. The aim is to identify a combination that is best suited for the differentiation of human neurons. RUCDR and NYSCF created lines from the same three Simons VIP participants, using fibroblasts, erythroblasts or lymphocytes and different re-programming methods (episomal plasmids, Sendai virus or modified RNAs) (Table 2). We will update our website as new results from this study become available.
Table 1. iPSC lines available from the SSC
Table 2. iPSC lines available from the Simons VIP
| Genetic event | ASD diagnosis | Number of donors for whom lines are available | Labs that generated iPSCs | Source cells | References |
|---|---|---|---|---|---|
| 16p11.2 duplication | No | 3 | Ricardo Dolmetsch | fibroblasts | unpublished |
| 16p11.2 deletion | No | 8 | Ricardo Dolmetsch | fibroblasts | unpublished |
| 16p11.2 deletion | Yes | 3 | RUCDR and NYSCF | fibroblasts, erythroblasts or CD4+ lymphocytes |
unpublished |
A spreadsheet with detailed information about all available lines is available for download here.
Ordering Instructions:
Aliquots of all lines are stored at the SFARI biorepository at RUCDR. Prices are available here.
Quality control data are available for some of the lines upon request.
To order, register with SFARI Base: click here for detailed registration instructions.
Please direct all questions about ordering to collections@sfari.org.
Note: Please carefully review the Researcher Distribution Agreement and sign the joinder agreement. In addition, institutional review board approval or exemption is needed for all planned studies with iPSC lines.
Current and past SFARI-funded projects that created and/or characterized iPSCs
In addition to the creation of lines from the SSC and Simons VIP, SFARI has supported multiple investigators to create iPSC lines from individuals with an autism diagnosis and a defined genetic event linked to that diagnosis. More recently, we have also funded the generation of iPSC lines in which a genetic mutation that is linked to autism has been introduced with CRISPR/CAS9 gene editing.
Current and past SFARI-funded grants involving iPSC studies are listed below. More information about the availability of these lines will be available on our website in the coming months.
- George Church, Ph.D.
Human gene editing and in situ sequencing of neuronal microcircuit arrays
Year Awarded: 2015
- Ricardo Dolmetsch, Ph.D.
Using iPS cells to study genetically defined patients with autism
Year Awarded: 2009
- James Gusella, Ph.D.
Molecular consequences of strong-effect autism mutations, including 16p11.2
Year Awarded: 2014
iPSC publications deriving from this work: Tai et al.3.
- Rudolph Jaenisch, M.D.
Genetically defined stem cell models of Rett and fragile X syndromes
Year Awarded: 2011
iPSC publications deriving from this work: Li et al.4.
- Maria Karayiorgou, M.D.
Investigating the effects of chromosome 22q11.2 deletions
Year Awarded: 2010
- Anne Marion Taylor, Ph.D.
RNA expression at human fragile X synapses
Year Awarded: 2013
- Hongjun Song, Ph.D.
Studying the neural development of patient-derived stem cells
Year Awarded: 2011
Understanding brain disorders related to the 15q11.2 chromosomal region
Year Awarded: 2014
iPSC publications deriving from this work: Yoon et al.5.
- Eric Ullian, Ph.D.
Role of myelinating cells in autism
Year Awarded: 2013
- Flora Vaccarino, M.D.
Integrated approach to the neurobiology of autism spectrum disorders
Year Awarded: 2009
iPSC publications deriving from this work: Mariani et al.6.
- Lauren Weiss, Ph.D. and Eric Ullian, Ph.D.
Delineating the role of RAS/MAPK signaling in 16p11.2 CNV cellular phenotypes
Year Awarded: 2015
- Feng Zhang, Ph.D.
Cellular models for autism de novo mutations using human stem cells
Year Awarded: 2015
References
- 1.Mariani J. et al. Cell 162, 375-90 (2015) PubMed
- 2.Mariani J. et al. Cell 162, 375-90 (2015) PubMed
- 3.Tai D.J. et al. Nat. Neurosci. 19, 517-522 (2016) PubMed
- 4.Li Y. et al. Cell Stem Cell 13, 446-458 (2013) PubMed
- 5.Yoon K.J. et al. Cell Stem Cell 15, 79-91 (2014) PubMed
- 6.Mariani J. et al. Cell 162, 375-90 (2015) PubMed