Engineering brain assembloids to interrogate human neural circuits

Yuki Miura, Min-Yin Li, Omer Revah, Se-Jin Yoon, Genta Narazaki, Sergiu P. Pașca

Published: 2022-01-05 DOI: 10.1038/s41596-021-00632-z

human pluripotent stem cells

brain assembloids

neural circuits

long-range neuronal connectivity

neurodevelopmental disorders

AI 解读

Generation of mouse–human chimeric embryos

Genome-wide quantification of transcription factor binding at single-DNA-molecule resolution using methyl-transferase footprinting

Generation of CRISPR–Cas9-mediated genetic knockout human intestinal tissue–derived enteroid lines by lentivirus transduction and single-cell cloning

A puromycin-dependent activity-based sensing probe for histochemical staining of hydrogen peroxide in cells and animal tissues

Decoding personal biotic and abiotic airborne exposome

A clinically relevant model of focal embolic cerebral ischemia by thrombus and thrombolysis in rhesus monkeys

Bioengineering human intestinal mucosal grafts using patient-derived organoids, fibroblasts and scaffolds

Biomimetic tail-to-head terpene cyclizations using the resorcin[4]arene capsule catalyst

Neuroscience robotics for controlled induction and real-time assessment of hallucinations

Scanorama: integrating large and diverse single-cell transcriptomic datasets

Single-cell RNA sequencing (scRNA-seq)（单细胞RNA测序）

Data integration（数据集成）

Heterogeneity（异质性）

查看全部

Sections

Figures

References

The development of neural circuits involves wiring of neurons locally following their generation and migration, as well as establishing long-distance connections between brain regions. Studying these developmental processes in the human nervous system rem
Introduction
Materials
Procedure
Troubleshooting
Timing
Anticipated results
- References
References
ACKNOWLEDGMENTS

Winnubst, J. et al. Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain. Cell 179, 268–281.e13 (2019).
Kostovic, I., Rados, M., Kostovic-Srzentic, M. & Krsnik, Z. Fundamentals of the development of connectivity in the human fetal brain in late gestation: from 24 weeks gestational age to term. J. Neuropathol. Exp. Neurol. 80, 393–414 (2021).
Kaiser, T. & Feng, G. Modeling psychiatric disorders for developing effective treatments. Nat. Med. 21, 979–988 (2015).
Pasca, S. P. The rise of three-dimensional human brain cultures. Nature 553, 437–445 (2018).
Velasco, S., Paulsen, B. & Arlotta, P. 3D brain organoids: studying brain development and disease outside the embryo. Annu. Rev. Neurosci. 43, 375–389 (2020).
Birey, F. et al. Assembly of functionally integrated human forebrain spheroids. Nature 545, 54–59 (2017).
Bagley, J. A., Reumann, D., Bian, S., Levi-Strauss, J. & Knoblich, J. A. Fused cerebral organoids model interactions between brain regions. Nat. Methods 14, 743–751 (2017).
Xiang, Y. et al. Fusion of regionally specified hPSC-derived organoids models human brain development and interneuron migration. Cell Stem Cell 21, 383–398.e7 (2017).
Sloan, S. A., Andersen, J., Pasca, A. M., Birey, F. & Pasca, S. P. Generation and assembly of human brain region-specific three-dimensional cultures. Nat. Protoc. 13, 2062–2085 (2018).
Yoon, S.-J. et al. Reliability of human cortical organoid generation. Nat. Methods 16, 75–78 (2019).
Miura, Y. et al. Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells. Nat. Biotechnol. 38, 1421–1430 (2020).
Shepherd, G. M. Corticostriatal connectivity and its role in disease. Nat. Rev. Neurosci. 14, 278–291 (2013).
Welch, J. M. et al. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 448, 894–900 (2007).
Peca, J. et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472, 437–442 (2011).
Milad, M. R. & Rauch, S. L. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn. Sci. 16, 43–51 (2012).
Sharma, A., Sances, S., Workman, M. J. & Svendsen, C. N. Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery. Cell Stem Cell 26, 309–329 (2020).
Xiang, Y. et al. hESC-derived thalamic organoids form reciprocal projections when fused with cortical organoids. Cell Stem Cell 24, 487–497.e7 (2019).
Andersen, J. et al. Generation of functional human 3D cortico-motor assembloids. Cell 183, 1913–1929.e26 (2020).
Cakir, B. et al. Engineering of human brain organoids with a functional vascular-like system. Nat. Methods 16, 1169–1175 (2019).
Marton, R. M. et al. Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures. Nat. Neurosci. 22, 484–491 (2019).
Strano, A., Tuck, E., Stubbs, V. E. & Livesey, F. J. Variable outcomes in neural differentiation of human PSCs arise from intrinsic differences in developmental signaling pathways. Cell Rep. 31, 107732 (2020).
Micali, N. et al. Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates. Cell Rep. 31, 107599 (2020).
Button, K. S. et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat. Rev. Neurosci. 14, 365–376 (2013).
Pasca, S. P. et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat. Med. 17, 1657–1662 (2011).
Tian, Y. et al. Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. Genome Med. 6, 75 (2014).
Sun, Y. et al. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients. eLife 5, e13073 (2016).
Susaki, E. A. et al. Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157, 726–739 (2014).
Tainaka, K. et al. Chemical landscape for tissue clearing based on hydrophilic reagents. Cell Rep. 24, 2196–2210.e9 (2018).
Klapoetke, N. C. et al. Independent optical excitation of distinct neural populations. Nat. Methods 11, 338–346 (2014).
de Leeuw, C. N. et al. rAAV-compatible MiniPromoters for restricted expression in the brain and eye. Mol. Brain 9, 52 (2016).
Chetty, S. et al. A simple tool to improve pluripotent stem cell differentiation. Nat. Methods 10, 553–556 (2013).
Ishikawa, D. et al. Fluorescent pipettes for optically targeted patch-clamp recordings. Neural Netw. 23, 669–672 (2010).

Engineering brain assembloids to interrogate human neural circuits

推荐阅读