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Peng Jiang Lab

Stem Cell Disease Modeling

Down syndrome (DS) is the most common genetic cause of intellectual disability and developmental delay, and it affects one in every 700-800 live births. Also called Trisomy 21, this condition occurs when an individual has 3 copies of human chromosome 21 (HSA21). Currently, there are no approved treatments to improve cognitive function in patients with DS. One of the major hurdles in developing treatments is the lack of knowledge on the precise mechanism underlying the cognitive impairments. Our current knowledge on the neuropathophysiology of DS is mainly gained from studies in transgenic mouse models and human DS fetal brain tissues. However, these strategies have limited utility because human tissues are relatively inaccessible and the mouse models only demonstrate an incomplete trisomy of HSA21.

The advent of induced pluripotent stem cell (iPSC) technology has provided a new approach to the establishment of human cellular models for studying the pathogenesis of neurodevelopmental and neurodegenerative diseases. We have generated human iPSCs directly from DS patients and differentiated them to patients’ own brain cells. Moreover, we have established 2-dimensional (2D) stem cell neural differentiation model, 3D cerebral organoid model as well as in vivo humanized chimeric mouse brain model to study the disease mechanisms (Figure 1).

Figure 1

Imbalance of excitatory and inhibitory neurotransmission is one of the major causes underlying the cognitive deficit in many neurological disorders, including DS. Currently, we focus on studying how DS astroglia regulate the formation of functional excitatory synapses, how the normal development of inhibitory GABAergic neurons is changed by expression of the genes triplicated in HSA21, and how these cellular and molecular abnormalities collectively contribute to abnormal synaptic plasticity and cognitive deficit of DS. We also expect to establish these stem cell studies as a template for the investigation of other neurological diseases, such as autism and schizophrenia.    

Contact Peng Jiang

Peng Jiang
Department of Cell Biology and Neuroscience
Rutgers University
Nelson Biology Labs
604 Allison Road, Room B209
Piscataway, NJ 08854-8082

(848) 445-3118 Lab

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Nelson Biology Labs
604 Allison Road
Piscataway, NJ 08854-8082
(848) 445-3471

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