Download Skin cells to brain cells

Skin cells to brain cells
Simons VIP Family Meeting
Orlando, Florida
July 19th – 21st, 2013
Dr. Aditi Deshpande
Postdoctoral fellow
University of California San Francisco
Background
Human development
Specialized
cells
Oocyte
Sperm
Organs
Human
Embryo
• Genetic information to make a human is contained in a single cell
• This cell divides to give rise to a multi-celled embryo
• As development progresses, cells become specialized
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Pluripotent
stem cells
Background
How do we study 16p11.2 deletions/duplications?
•
The mechanism is not determined
•
Limited treatment strategies and targets to test drugs
•
Classical approaches to study human neurodevelopmental disorders •
Animal models
•
Post mortem studies in humans
•
Imaging studies in humans
Background
Clipart.com/78873
But to find out the precise disruption and design a
treatment, we need to study the specialized cells that are
malfunctioning
Background
• Cells are highly specialized
• But every cell contains the same genetic information
Hair
Neurons??
Neurons??
Skin
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Can we convert one specialized cell type into another??
Induced pluripotent stem cells
Yes!!
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iPSC technology
Reprogramming
Skin cells
Induced pluripotent
stem cells (iPSCs)
Background
iPSC technology •
Allows cells to “go back in time”
•
Acquire a stem cell-like state
Skin cells
Pluripotent
stem cells
Neurons
Organ
What are iPSCs?
Induced pluripotent stem cells (iPSCs) are •
Generated in the lab
•
Made from specialized cells of the body by “forced” expression of certain
proteins: induced
•
Able to be converted to many different cell types in the body: pluripotent
•
Able to multiply: self-renewing (stem cell)
Why iPSCs?
Non-invasive
iPSCs are a potentially infinite resource
They can be used to study human diseases and disorders affecting
different organs
Since they are derived from patients, they have the same genetic
information that contributes to the pathophysiology of the disease
Conversion of iPSCs to specialized cell type follows developmental
principles
They can be used to study the disease at different developmental
stages
The iPSCs technology
Drug screening
Disease models
Developmental
studies
16p11.2 CNV
ASDs
Down syndrome
Alzheimer’s disease
Parkinson’s disease
Diabetes
Adapted from http://www.bumc.bu.edu
iPSC technology provides an excellent platform to study human
diseases and disorders directly at the source, i.e. affected human cells
Modeling 16p11.2 deletion/duplication in a dish
Steps involved Skin cells
16p11.2
CNV carrier
iPSCs
Skin biopsy
Adapted from Brennand KJ et al, 2012
Skin cells
iPSC colony
Modeling 16p11.2 deletion/duplication in a dish
•
8-12 weeks
iPSCs
Day 3
Embryoid
bodies
Day 11
11
Day
Day 20
3
42
Neural
rosettes
Neurospheres
Day 20
Neurons
Day 42
Modeling 16p11.2 deletion/duplication in a dish
Neurite outgrowth assay
2
3
1
Summary
• iPSCs are artificial, pluripotent, self-renewing resource for obtaining
patient-derived specialized cells
• The iPSC technology can be used to generate neurons from 16p11.2
deletion and duplication carriers
Study the neurons with respect to
their development, growth, migration
and electrical properties; compare to
controls
Design therapeutic strategies
Neurons
Test drugs for treatment
The goal is to better understand consequences of deletion
or duplication of 16p11.2 in order to prevent or treat them
Acknowledgements
Dr. Lauren Weiss
Zhi Yong Wu (Tony)
Dr. Erika Yeh
and other lab members
Dr. Erik Ullian
Dr. Gemma Rooney
Simons Foundation