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Author Alfred Sun

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Lewy Body-like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α-Synuclein Mutations.

Junghyun Jo, Lin Yang, Hoang-Dai Tran, Weonjin Yu, Alfred Xuyang Sun, Ya Yin Chang, Byung Chul Jung, Seung-Jae Lee, Tzuen Yih Saw, Bin Xiao, Audrey Tze Ting Khoo, Lai-Ping Yaw, Jessica Jiaxin Xie, Hidayat Lokman, Wei-Yi Ong, Grace Gui Yin Lim, Kah-Leong Lim, Eng-King Tan, Huck-Hui Ng, Hyunsoo Shawn Je,

<h4>Objective</h4>We utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn- and Lewy body-related pathologies and the process of neurodegeneration in the hMLO model.<h4>Methods</h4>We generated and ... Read more >>

Ann Neurol (Annals of neurology)
[2021, 90(3):490-505]

Cited: 0 times

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Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids.

Jing-Han Ng, Alfred Sun, Hyunsoo Shawn Je, Eng-King Tan,

Neuropsychiatric manifestations of coronavirus disease 2019 (COVID-19) have been increasingly recognized. However, the pathophysiology of COVID-19 in the central nervous system remains unclear. Brain organoid models derived from human pluripotent stem cells are potentially useful for the study of complex physiological and pathological processes associated with severe acute respiratory syndrome ... Read more >>

Neuroscientist (The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry)
[2021, :10738584211015136]

Cited: 0 times

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Evaluating Capture Sequence Performance for Single-Cell CRISPR Activation Experiments.

Xin Yi Choo, Yu Ming Lim, Khairunnisa Katwadi, Lynn Yap, Karl Tryggvason, Alfred Xuyang Sun, Shang Li, Lusy Handoko, John F Ouyang, Owen J L Rackham,

The combination of single-cell RNA sequencing with CRISPR inhibition/activation provides a high-throughput approach to simultaneously study the effects of hundreds if not thousands of gene perturbations in a single experiment. One recent development in CRISPR-based single-cell techniques introduces a feature barcoding technology that allows for the simultaneous capture of mRNA ... Read more >>

ACS Synth Biol (ACS synthetic biology)
[2021, 10(3):640-645]

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Potassium channel dysfunction in human neuronal models of Angelman syndrome.

Alfred Xuyang Sun, Qiang Yuan, Masahiro Fukuda, Weonjin Yu, Haidun Yan, Grace Gui Yin Lim, Mui Hoon Nai, Giuseppe Alessandro D'Agostino, Hoang-Dai Tran, Yoko Itahana, Danlei Wang, Hidayat Lokman, Koji Itahana, Stephanie Wai Lin Lim, Jiong Tang, Ya Yin Chang, Menglan Zhang, Stuart A Cook, Owen J L Rackham, Chwee Teck Lim, Eng King Tan, Huck Hui Ng, Kah Leong Lim, Yong-Hui Jiang, Hyunsoo Shawn Je,

Disruptions in the ubiquitin protein ligase E3A (<i>UBE3A</i>) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, ... Read more >>

Science (Science (New York, N.Y.))
[2019, 366(6472):1486-1492]

Cited: 26 times

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PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction.

Wei Zhou, Dongrui Ma, Alfred Xuyang Sun, Hoang-Dai Tran, Dong-Liang Ma, Brijesh K Singh, Jin Zhou, Jinyan Zhang, Danlei Wang, Yi Zhao, Paul M Yen, Eyleen Goh, Eng-King Tan,

Coiled-coil-helix-coiled-coil-helix domain containing protein 2 (CHCHD2) mutations were linked with autosomal dominant Parkinson's disease (PD) and recently, Alzheimer's disease/frontotemporal dementia. In the current study, we generated isogenic human embryonic stem cell (hESC) lines harboring PD-associated CHCHD2 mutation R145Q or Q126X via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 ... Read more >>

Hum Mol Genet (Human molecular genetics)
[2019, 28(7):1100-1116]

Cited: 10 times

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Translational potential of human brain organoids.

Alfred X Sun, Huck-Hui Ng, Eng-King Tan,

The recent technology of 3D cultures of cellular aggregates derived from human stem cells have led to the emergence of tissue-like structures of various organs including the brain. Brain organoids bear molecular and structural resemblance with developing human brains, and have been demonstrated to recapitulate several physiological and pathological functions ... Read more >>

Ann Clin Transl Neurol (Annals of clinical and translational neurology)
[2018, 5(2):226-235]

Cited: 10 times

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3D neural tissue models: From spheroids to bioprinting.

Pei Zhuang, Alfred Xuyang Sun, Jia An, Chee Kai Chua, Sing Yian Chew,

Three-dimensional (3D) in vitro neural tissue models provide a better recapitulation of in vivo cell-cell and cell-extracellular matrix interactions than conventional two-dimensional (2D) cultures. Therefore, the former is believed to have great potential for both mechanistic and translational studies. In this paper, we review the recent developments in 3D in vitro neural tissue ... Read more >>

Biomaterials (Biomaterials)
[2018, 154:113-133]

Cited: 44 times

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Towards better cellular replacement therapies in Parkinson disease.

Alfred Xuyang Sun, Eng-King Tan,

J Neurosci Res (Journal of neuroscience research)
[2018, 96(2):219-221]

Cited: 0 times

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Direct Induction and Functional Maturation of Forebrain GABAergic Neurons from Human Pluripotent Stem Cells.

Alfred Xuyang Sun, Qiang Yuan, Shawn Tan, Yixin Xiao, Danlei Wang, Audrey Tze Ting Khoo, Levena Sani, Hoang-Dai Tran, Paul Kim, Yong Seng Chiew, Kea Joo Lee, Yi-Chun Yen, Huck Hui Ng, Bing Lim, Hyunsoo Shawn Je,

Gamma-aminobutyric acid (GABA)-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that ... Read more >>

Cell Rep (Cell reports)
[2016, 16(7):1942-1953]

Cited: 35 times

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Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons.

Junghyun Jo, Yixin Xiao, Alfred Xuyang Sun, Engin Cukuroglu, Hoang-Dai Tran, Jonathan Göke, Zi Ying Tan, Tzuen Yih Saw, Cheng-Peow Tan, Hidayat Lokman, Younghwan Lee, Donghoon Kim, Han Seok Ko, Seong-Oh Kim, Jae Hyeon Park, Nam-Joon Cho, Thomas M Hyde, Joel E Kleinman, Joo Heon Shin, Daniel R Weinberger, Eng King Tan, Hyunsoo Shawn Je, Huck-Hui Ng,

Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a ... Read more >>

Cell Stem Cell (Cell stem cell)
[2016, 19(2):248-257]

Cited: 208 times

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Kinetic analysis of npBAF to nBAF switching reveals exchange of SS18 with CREST and integration with neural developmental pathways.

Brett T Staahl, Jiong Tang, Wei Wu, Alfred Sun, Aaron D Gitler, Andrew S Yoo, Gerald R Crabtree,

During the development of the vertebrate nervous system, neural progenitors divide, generate progeny that exit mitosis, and then migrate to sites where they elaborate specific morphologies and synaptic connections. Mitotic exit in neurons is accompanied by an essential switch in ATP-dependent chromatin regulatory complexes from the neural progenitor Brg/Brm-associated factor ... Read more >>

J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience)
[2013, 33(25):10348-10361]

Cited: 52 times

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MicroRNAs: regulators of neuronal fate.

Alfred X Sun, Gerald R Crabtree, Andrew S Yoo,

Mammalian neural development has been traditionally studied in the context of evolutionarily conserved signaling pathways and neurogenic transcription factors. Recent studies suggest that microRNAs, a group of highly conserved noncoding regulatory small RNAs also play essential roles in neural development and neuronal function. A part of their action in the ... Read more >>

Curr Opin Cell Biol (Current opinion in cell biology)
[2013, 25(2):215-221]

Cited: 101 times

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MicroRNA-mediated conversion of human fibroblasts to neurons.

Andrew S Yoo, Alfred X Sun, Li Li, Aleksandr Shcheglovitov, Thomas Portmann, Yulong Li, Chris Lee-Messer, Ricardo E Dolmetsch, Richard W Tsien, Gerald R Crabtree,

Neurogenic transcription factors and evolutionarily conserved signalling pathways have been found to be instrumental in the formation of neurons. However, the instructive role of microRNAs (miRNAs) in neurogenesis remains unexplored. We recently discovered that miR-9* and miR-124 instruct compositional changes of SWI/SNF-like BAF chromatin-remodelling complexes, a process important for neuronal ... Read more >>

Nature (Nature)
[2011, 476(7359):228-231]

Cited: 547 times

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Runx1 protects hematopoietic stem/progenitor cells from oncogenic insult.

Lena Motoda, Motomi Osato, Namiko Yamashita, Bindya Jacob, Lynnette Q Chen, Masatoshi Yanagida, Hiroshi Ida, Hee-Jun Wee, Alfred X Sun, Ichiro Taniuchi, Dan Littman, Yoshiaki Ito,

The RUNX1/AML1 gene encodes a transcription factor essential for the generation of hematopoietic stem cells and is frequently targeted in human leukemia. In human RUNX1-related leukemias, the RAS pathway is often concurrently mutated, but the mechanism of the synergism remains elusive. Here, we found that inactivation of Runx1 in mouse ... Read more >>

Stem Cells (Stem cells (Dayton, Ohio))
[2007, 25(12):2976-2986]

Cited: 48 times

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