Peng Jiang Lab

Stem Cell Disease Modeling

Down syndrome (DS) is the most common genetic origin of intellectual disability and is the single most common risk factor for early-onset Alzheimer’s disease (AD). Also called Trisomy 21, this condition occurs when an individual has 3 copies of human chromosome 21 (HSA21). The additional genetic material causes impairment in cognitive ability and physical growth and is often associated with other complications ranging from cardiac defects to hearing and vision problems. Most physical symptoms of DS can now be treated or alleviated, but there are no effective treatments that improve cognitive function. By the age of 40, people with DS will reliably develop amyloid plaques and neurofibrillary tangles, two pathological hallmarks of AD in the general population and the vast majority will develop AD dementia by their 60s. Therefore, understanding the molecular mechanisms underlying the abnormal brain development and early-onset AD in DS may assist with the development of novel treatments for intellectual disability and AD in this important population as well as for AD in general population.

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 human chimeric mouse brain model to study the disease mechanisms and develop novel therapeutics (Figure 1).

Representative publications (* co-corresponding author; # co-first author):

Kim H and Jiang P. Generation of Human Pluripotent Stem Cell-Derived Fused Organoids with Oligodendroglia and Myelin. STAR Protocols. 2021 Apr 7;2(2):100443.

Jiang, P., Turkalj, L., & Xu, R. (2020). High-Fidelity Modeling of Human Microglia with Pluripotent Stem Cells. Cell Stem Cell, 26, 629-631.

Xu R, Li X, Boreland AJ, Posyton A, Kwan K, Hart RP, Jiang P.  Human iPSC-derived mature microglia retain their identity and functionally integrate in the chimeric mouse brain. Nat Commun. 2020 Mar 27;11(1):1577.

Xu, R., Brawner, A. T., Li, S., Liu, J. J., Kim, H., Xue, H., Pang, Z. P., Kim, W. Y., Hart, R. P., Liu, Y., & Jiang, P. OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome. Cell Stem Cell. 2019 Jun 6;24(6):908-926.e8.
Commentary: Manley WF, Anderson. SA. Dosage Counts: Correcting Trisomy-21-Related Phenotypes in Human Organoids and Xenografts. Cell Stem Cell. 2019 Jun 6;24(6):835-836.
Commentary: Ming Yang. A bit too much Olig2 in Down’s syndrome. Science Translational Medicine 05 Jun 2019: Vol. 11, Issue 495, eaay1425
Kim, H., Xu, R., Padmashri, R., Dunaevsky, A., Liu, Y., Dreyfus, C. F., & Jiang, P. Pluripotent Stem Cell-Derived Cerebral Organoids Reveal Human Oligodendrogenesis with Dorsal and Ventral Origins. Stem Cell Reports, 2019 May 12, 890-905.
Qi D, Wu S, Lin H, Kuss MA, Lei Y, Krasnoslobodtsev A, Ahmed S, Zhang C, Kim HJ, Jiang P*, Duan B*. Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System. ACS Appl Mater Interfaces. 2018 Jul 10(26):21825-21835.
Wu, S., Xu, R., Duan, B*. and Jiang, P*. Three-dimensional hyaluronic acid hydrogel-based models for in vitro human iPSC-derived NPC culture and differentiation. Journal of Materials Chemistry B. 2017 Jun 5(21):3870-3878.
Chen C, Kim W, Jiang P. Humanized Neuronal Chimeric Mouse Brain Generated by Neonatally Engrafted Human iPSC-Derived Primitive Neural Progenitor Cells. Journal of Clinical Investigation Insight. 2016 Nov 1(19):e88632.
Chen C#, Jiang P#, Xue H, Peterson SE, Tran HT, McCann AE, Parast MM, Li S, Pleasure DE, Laurent LC, Loring JF, Liu Y, Deng W. Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells. Nature Communications. 2014 Jul 18;5:4430

Figure 1

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