Peng Jiang Lab@Rutgers

Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies Papetti et al. discuss recent advances in understanding human neural development, aging, and disease uncovered through human-rodent chimeric brain models and examine their potential to drive progress ...

Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies: Neuron www.cell.com/neuron/fullt...

New approach methodologies: Don’t throw the baby out with the bathwater The NIH has recently called for expanding use of new approach methodologies (NAMs) to reduce use of animals in research. Arany discusses the need not to forget the irreplaceable aspects of animal rese...

All models have limitations. Animal models remain indispensable for neuroscience research. Meanwhile, chimeric brain models provide unique opportunities to study human neural cells with advanced maturation and functional integration in an in vivo brain environment.

www.cell.com/cell-metabol...

In this study, we developed a series of new chimeric brain models by combining different transgenic mouse lines with co-transplantation of human microglia and neural cells, enabling in vivo studies of human neuro–glia and glia–glia interactions.

Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions Jin et al. develop chimeric mouse brains containing human microglia, astroglia, oligodendroglia, and neurons, enabling direct interrogation of human neuron-glia interactions in vivo. These models reca...

Thrilled to share our new study published in @cp-cellreports.bsky.social, led by Mengmeng Jin, Ziyuan Ma, and Haiwei Zhang. Grateful for a wonderful collaboration with Dr. Steve Goldman, a pioneer in chimeric brain models and a leading expert in glial biology.

www.cell.com/cell-reports...

Thank you so much for highlighting our work!

A myeloid trisomy 21-associated gene variant is protective from Alzheimer’s disease Nature Neuroscience - Engineering human microglia with a Down-syndrome-linked myeloid gene variant resists tau-induced dysfunction and protects neurons in chimeric brains, offering proof of concept...

Explore our new study here, and Happy Thanksgiving to all!

Author’s link: rdcu.be/eRvdA

Rutgers Today article @rutgersupress.bsky.social @rutgersu.bsky.social:

www.rutgers.edu/news/inspire...

An idea we started in 2019 is now published in @natneuro.nature.com! Excited to share our new study: rdcu.be/eRvdA

Congrats to Mengmeng Jin and our team! Heartfelt thanks to all collaborators for their support, and to the reviewers for their insightful comments!

We also discuss technical challenges and share ideas to improve current models—making them more effective and broadly applicable.

We’re excited about the growing potential of chimeric brain models, and hope this piece sparks new ideas, collaborations, and progress in the field!

• Enable glial replacement strategies: studying interactions between diseased human glia and newly engrafted replacement human glia
• Study In vivo reprogramming of glia to neurons
• Combine with single-cell and functional assays to deepen the understanding of the human brain

• Reveal human-specific brain development & aging processes
• Uncover mechanisms of neurodevelopmental (e.g., autism) and neurodegenerative (e.g., Alzheimer’s) disorders

In this review, we center around one key idea: unlock.

How can chimeric brain models unlock the mysteries of human brain development, aging, and disease?

We discussed how these chimeric models can: 👇

Recently, with strong support from the team, we rebuilt it from scratch—and @cp-neuron.bsky.social gave it a home!

Big thanks to the reviewers for their thoughtful and constructive feedback!

This review was actually written once before (the section on methodological considerations for creating chimeric models is shown in the image below), but it didn’t make it to publication at the time.

Since starting my lab, we’ve made chimeric brain models a core focus. Our team published studies on the human microglia chimeric brain model and applied chimeric models to investigate disease mechanisms.

I was inspired by Dr. Suchun Zhang’s work on differentiating human PSCs + transplanting them into mice, and Dr. Steven Goldman’s work on human oligodendroglia taking over mouse brains.

We discussed the idea of chimeric models in our 2014 Nat Commun paper 👇

The idea for this review has been a long time in the making.

Back during my postdoc, I often discussed “no brainer” mice (mice lacking cortical structures) with my mentor Dr. Wenbin Deng, which sparked my curiosity about human cell engraftment in the mouse brain.

Thrilled to share our review just published in @cp-neuron.bsky.social ! 🎉
Big shoutout to Ava, Mengmeng, and our entire team!
authors.elsevier.com/a/1k-uh3BtfH...

Hopefully a little inspiration for our trainees...this was led by an amazing postdoc at UPitt..Dr. Jean Liou

Advancements in 3D models for studying human iPSC-microglia: Insights into neurodevelopment and neurological disorders Microglia are immune cells of the central nervous system, playing a vital role in brain development, homeostasis, and disease. When these cells become…

Advancements in 3D models for studying human iPSC-microglia: Insights ... www.sciencedirect.com/science/arti...

Human longevity and Alzheimer’s disease variants act via microglia and oligodendrocyte gene networks Graham et al. show that Alzheimer's disease-associated genetic variants are enriched in gene networks expressed by microglia and oligodendrocytes during ag

Human longevity and Alzheimer’s disease variants act via microglia and oligodendrocyte gene networks
academic.oup.com/brain/advanc...

Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer’s disease - Nature Neuroscience This article discusses a puzzling issue in brain pathology: why brain-resident microglia are insufficient for protection, and why myeloid cells are needed from the periphery. Several strategies are pr...

www.nature.com/articles/s41...