Stem Cell Modeling Expertise
What the UCSB CIRM SRL Offers:
- Facility for Cell Culture and Analysis
The UCSB CIRM SRL offers cell and tissue culture facilities that include biosafety cabinets, centrally supplied CO2 incubators, mycoplasma tested, sterile plasticware, as well as refrigerators, freezers, -80 freezers, and liquid nitrogen cell storage protected by full-time monitoring. In addition, we offer an array of advanced instrumentation to characterize and analyze your cells of interest. The facility is turn-key ready for new users who wish to carry out stem cell and gene therapy research.
- Novel hPSC Lines
Patient-derived hiPSC and CRSPR-engineered hPSC lines for modeling neural development and disease.
The SRL offers a number of cell lines that have been generated and characterized by making iPSC from patient samples, CRSPR engineering of hESC and iPSC lines, and differentiating specific cell types related to neural disease. 89 cell lines that are sharable (not proprietary) are listed here Cell Lines.
These lines fall into 5 categories:
- Neural Signaling Pathways in Neural Development; DNA Repair during Neural Differentiation and Disease.
Investigators in the Wilson, Streichan and Dey labs are combining light-switchable (optogenetic) molecules to precisely tune inputs to molecular and cellular networks involved in neural development. This approach is coupled with the development of a variety of fluorescent output reporters. Lines developed include constructs to regulate WNT and ERK signaling, with corresponding output reporters. These are invaluable tools for studying neural cell signaling in stem cell-derived cells, as well as many other differentiation pathways. We believe these optogenetic lines will be of interest to many stem cell researchers in California. The Richardson Lab is investigating regulation of repair in various (mostly neural) diseases using stem-cell based models. They have engineered lines with DOX-inducible CAS9 to give rise to mutations relevant to neural diseases. - Neurodegenerative Diseases /Alzheimer’s Disease / Frontotemporal Dementia.
The Kosik lab has made available hiPSC harboring mutations that cause neurodegeneration / Alzheimer’s Disease. In collaboration with the Tau Consortium have generated a number of cell lines with tau mutations linked to disease. (Karch et al., 2019) These lines now make it possible to study the disease processes in human cells and human brain organoids (Glasauer et al., 2022). Another focus of Kosik’s work is TAR DNA-binding protein 43 (TDP-43) where mutations are associated with frontotemporal dementia, Alzheimer’s Disease, and amyotrophic lateral sclerosis. In addition, iPSC APOE lines with different apolipoprotein E (APOE) isoforms and iPSC with CRSPR-engineered presenilin-1 (PSEN-1) mutations that cause early onset AD are available. - Cri du chat Syndrome, Williams Syndrome, Peroxisomal Import.
Cri du chat is caused by deletions in chromosome 5 and we have generated multiple cri du chat iPSCs lines. Williams syndrome is caused by a large deletion of genes on chromosome 7 (Lalli et al., 2016). We have generated multiple cell lines using CRSPR I to model Zellweger’s Syndrome, and PEX gene defects. - Age-Related Macular Degeneration / Retinitis Pigmentosa / Danon Disease.
Lines have been engineered to express AMD, RP and Danon -associated mutations. - Allen Cell Lines.
Allen Institute scientists have been growing the portfolio of 56 hIPScell lines harboring fluorescent protein fusion constructs that light up 43 individual organelles/structures. UCSB has partnered with the Allen Institute to make these cell lines available via our core facility.
- Neural Signaling Pathways in Neural Development; DNA Repair during Neural Differentiation and Disease.
- Integrated Embryo Models
Methods for modeling early neural development.
Integrated Embryo Models are organized three-dimensional cell assemblages derived from pluripotent stem cells that recapitulate early human development. https://www.cirm.ca.gov/wp-content/uploads/2024/05/CIRM-SWG-Summary-and-Guidance-for-Oversight-of-Human-Stem-Cell-Based-Embryo-Models.pdf
The Wilson, Dey and Streichan labs have pioneered new methods for generation of human 2D and 3D “gastruloids” to allow study of gastrulation and neural tube formation.
- Access to Advanced Imaging, Materials Analysis, and High-Content Screening at Other Shared UCSB Core Facilities
The Neuroscience Research Institute (NRI) and the Department of Molecular, Cellular and Developmental Biology (MCDB) jointly operate a shared core microscopy facility. https://microscopy.nri.ucsb.edu/ . Via our CIRM SRL, we offer access to this facility.
Instrumentation includes four confocal instruments all with environmental chambers. Additionally, the core provides: a Zeiss Z.1 Lightsheet microscope with 6 laser lines and dual sCMOS camera system, a JEOL transmission electron microscope, and 5 research grade compound microscopes equipped with fluorescence, phase, DIC, darkfield, and bright field capabilities. A novel new instrument, the Nanolive 3D Cell Explorer, offers label-free low photodamage imaging for long-term timelapse imaging.Via use of the CIRM SRL, we can offer access the UCSB Biofoundry (https://exfab.engineering.ucsb.edu/ ). The foundry boasts a high-throughput drug screening facility capable of screening over 400,000 compounds, Furthermore, it is equipped with tools for genome-wide CRISPR interference (CRISPRi) and activation (CRISPRa) applications, and high-throughput ELISAs. UCSB’s foundry excels with ultra-high-content imaging capabilities, enabling detailed visualization of cells, organoids, and both 2D and 3D tissue constructs using confocal fluorescence microscopy.
Stem cell research at the UC Santa Barbara Core includes multiple efforts to develop materials for encapsulation and scaffolding for cells. We are happy to share this expertise with stem cell researchers throughout the state. We can also provide access to the Materials Research Lab (MRL), an advanced materials core. (www.mrl.ucsb.edu).
