A striking feature of the nervous system is its enormous cellular diversity. The Yang laboratory seeks to understand how the nervous system achieves its extraordinary cellular and functional complexity. To study these fundamental questions and associated brain disorders, we direct the differentiation of stem cells into diverse types of brain cells such as neurons, astrocytes, oligodendrocytes and microglia. Although reductionist in nature, this system allows us to reconstitute human nervous system in a dish and elucidate the underlying signaling interactions, cellular information processing, and gene expression regulation that govern basic activities of cells and coordinates all cell actions.
In the long term, our work aims at developing approaches and employ state-of-the-art stem cell biology, genome engineering, and neuroscience approaches to understand and modulate the neuronal function in neuropsychiatric diseases. We are particularly interested in understanding how disease associated risk variants in non-coding regions contribute to pathogenesis of multiple neuropsychiatric disorders including autism spectrum disorder, bipolar disorder and schizophrenia
Cell fate in the nervous system
We have pioneered the transcription factor mediated (trans-)differentiation of non-neural human cells, including fibroblasts and pluripotent stem cells, into multiple neural lineages including neurons and glial cells. Our goal is to investigate the fundamental events underlying the progression of cell fate specification and ultimately to recreate the cell types of the central nervous system from human pluripotent stem cells for research and potential use in clinical therapies.
Non-coding regions and human psychiatric diseases
Advances in human genetics and next-generation sequencing have permitted the identification of a stunning number of genetic variants that are linked to autism spectrum disorder (ASD), providing a platform for unraveling the causal chain of events that result in the disorder. However, the availability of data is not synonymous with the presence of meaning. Indeed, the challenge researchers are facing now is the derivation of biological meaning post-GWAS. Particularly, an increasing number of risk-associated variants are found in non-coding sequences. We use stem cell modeling system, genome engineering, CRISPR-mediated epigenetic editing, and state-of-the-art single-cell sequencing technology to determine the molecular impact of such non-coding sequence alterations.
Yang N, Chanda S, Marro S, Ng YH, Janas JA, Haag D, Ang CE, Tang Y, Flores Q, Mall M, Wapinski O, Li M, Ahlenius H, Rubenstein JL, Chang HY, Buylla AA, Südhof TC, Wernig M. Generation of pure GABAergic neurons by transcription factor programming. Nat Methods. 2017 Jun;14(6):621-628.
Yang N, Wernig M. Harnessing the stem cell potential: a case for neural stem cell therapy. Nat Med. 2013 Dec;19(12):1580-1.
Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, Hawkins JS, Geissler R, Barres BA, Wernig M. Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol. 2013 May;31(5):434-9.
Yang N, Dong Z, Guo S. Fezf2 Regulates Multilineage Neuronal Differentiation through Activating Basic Helix-Loop-Helix and Homeodomain Genes in the Zebrafish Ventral Forebrain. J Neurosci. 2012 Aug 8;32(32):10940-8.
Dong Z, Yang N, Chitnis A, Guo S. Intra-lineage directional Notch signaling regulates self-renewal ad differentiation of asymmetrically dividing radial glia. Neuron 2012 Apr 12;74(1):65-78.
Yang N, Ng YH, Pang ZP, Südhof TC, Wernig M. Induced neuronal cells: how to make and define a neuron. Cell Stem Cell. 2011 Dec 2;9(6):517-25.
Marro S, Pang ZP, Yang N, Tsai MC, Qu K, Chang HY, Südhof TC, Wernig M. Direct Lineage Conversion of Terminally Differentiated Hepatocytes to Functional Neurons. Cell Stem Cell. 2011 2011 Oct 4;9(4):374-82.
Pang ZP*, Yang N*, Vierbuchen T*, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M. Induction of human neuronal cells by defined transcription factors. Nature. 2011 May 26;476(7359):220-3.
We welcome postdoctoral applicants who are interested in applying pluripotent stem cell models to address basic mechanistic questions in the development, function and disease of human nervous system. Applicants with expertise in genomics, differentiation of pluripotent stem cells, or neural development/neuroscience are of particular interest at this time. Interested candidates should send their CV and names/contact information of 3 potential references to Dr. Nan Yang.