Advances in Single Cell Genomics to Study Brain Cell Types

单细胞在脑科学方面的应用

Session 1: Deciphering the Cellular Landscape of the Brain Using Single Cell Transcriptomics

Single cell/nucleus transcriptomics has emerged as a powerful approach to classify cell types and dynamic cell states in any multicellular organ or organism. By measuring gene expression in single cells in a genome-wide manner, one obtains a highly multidimensional molecular signature of each cell, which enables identification of cellular diversity and dynamic changes in the healthy and diseased brain.

Evan Macosko, Bosiljka Tasic, and Naomi Habib will present various methods to perform single cell and nucleus RNA-sequencing in brain tissue, computational approaches to analyze the data, and examples of applications in the mouse and human brain. A short Q&A will follow presentations.

Evan Macosko, MD, PhD
Broad Institute of MIT and Harvard
Evan Macosko is an assistant professor of psychiatry at Harvard Medical School and a group leader in the Stanley Center at the Broad Institute. Macosko's newly established lab focuses on developing new technologies in genomics to more deeply understand brain function and dysfunction. He earned his PhD in neuroscience from Rockefeller University and MD from Weill Cornell Medical College. He completed psychiatry residency at McLean and Massachusetts General Hospitals and postdoctoral training at Harvard Medical School.

讲了一些比较基础的方法

Boslijka Tasic, PhD
Allen Institute for Brain Science
Bosiljka Tasic is an Associate Director of Molecular Genetics at the Allen Institute for Brain Science in Seattle. She is interested in molecularly guided cell classification in the mouse nervous system and its implications for mouse brain function in health and disease. She completed her postdoctoral studies with Liqun Luo at Stanford, and received her PhD in Biochemistry under Tom Maniatis at Harvard.

Naomi Habib, PhD
Broad Institute of MIT and Harvard
Naomi Habib is a postdoctoral fellow at the Broad Institute of Massachusetts Institute of Technology and Harvard University working with Dr. Feng Zhang and Dr. Aviv Regev. Habib's research focuses on understanding the cellular and molecular mechanisms of degeneration and regeneration in the adult and aging brain. She is a pioneer in single nucleus RNA-sequencing technologies and their applications to study cellular diversity and molecular processes in the brain. Habib earned her BS, MS, and PhD in computational biology from the Hebrew University of Jerusalem in Israel.

这个大佬货很多，和张锋、aviv 都有合作，大佬啊。

Session 2: Single Cell Epigenomics Uncovers Gene Regulatory Diversity in Mammalian Brains

The epigenome is an ensemble of chemical modifications to DNA and chromatin that affects gene regulation. Genome-wide mapping of epigenomic signatures is one of the most effective approaches for identifying gene regulatory elements, such as enhancer sequences.

Chongyuan Luo and Sebastian Preissl will introduce the utility of single cell epigenomic approaches — such as DNA methylation profiling and chromatin accessibility profiling — that have demonstrated robust classifications of brain cell types and enabled the mapping of the regulatory landscape for virtually all brain cell populations. These approaches provide opportunities to determine the cell-type specific functions of non-coding sequences and decipher their contribution to brain diseases. A short Q&A will follow presentations.

Chongyuan Luo, PhD
HHMI & Salk Institute for Biological Sciences

Chongyuan Luo is a postdoctoral research associate in the Joe Ecker lab at Howard Hughes Medical Institute and Salk Institute for Biological Studies. His current research focuses on cell type diversity of healthy brains and genetic as well as epigenetic causes of brain diseases. Chongyuan earned his BS in biology from China Agricultural University and his PhD from Rutgers University.

讲调控的，单细胞层次。甲基化。全程都在秀CNS，大佬。

Sebastian Preissl, PhD
Center for Epigenomics, UCSD

Sebastian Preissl is an associate director of single cell genomics at the Center for Epigenomics at University of California, San Diego. As a postdoctoral fellow in Dr. Bing Ren's laboratory at the Ludwig Institute for Cancer Research he studied brain development and cancer using single cell ATAC-seq and single cell RNA-seq approaches.

单细胞ATAC-seq

Session 3: Spatial Transcriptomics of Neurons and Brain Circuits

空间定位

Brain cells have complex morphologies and are organized into complex networks in order to compute sensations, actions, decisions, and emotions. To understand this spatial organization and how it goes awry in brain disorder states, it is important to map transcripts — ideally at omic scale — throughout neurons and intact brain circuits in species such as mice and humans.

Ed Boyden, Long Cai, and Mats Nilsson will discuss cutting edge techniques, such as FISH and other sequencing technologies facilitated by strategies that de-crowd transcripts in dense tissues to permit the accurate assessment and mapping of transcripts in neurons in brain tissue. Such technologies enable the connection between the molecular world of cell types and cell states and the systems world of networks and circuits. These connections are key to understanding how brain computations are implemented, and how they might be repaired in states of disease. A short Q&A will follow presentations.

Ed Boyden, PhD
MIT

Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the Massachusetts Institute of Technology (MIT) Media Lab and the MIT McGovern Institute. He leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain, and applies them systematically to reveal ground truth principles of biological function as well as to repair these systems. Ed received his Ph.D. in neuroscience from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned.

Long Cai, PhD
California Institute of Technology

Long Cai is a research professor in biology within the division of biology and biological engineering at California Institute of Technology (Caltech). His research focuses on single cell systems biology and his lab uses super-resolution and live cell microscopy to study gene regulatory networks in cells and organisms. Cai earned his undergraduate degree in physics and chemistry from Harvard College and his PhD from Harvard University working with Sunney Xie on single molecular detection of gene expression in living cells. He completed his postdoctoral training with Michael Elowitz at Caltech as a Beckman Fellow.

Mats Nilsson, PhD
Stockholm University

Mats Nilsson is professor of biochemistry and molecular diagnostics in the department of biochemistry and biophysics at Stockholm University. He is also visiting professor at the department of immunology and genetics and pathology at Uppsala University, and scientific director at the Science for Life Laboratory. He earned his PhD in medical genetics.

Session 4: Multi-Feature Analysis and Integration for the Functional Dissection of Brain Cell Types

Understanding the diversity of brain cell types and the roles of cell types within brain circuits is an immense challenge in modern neuroscience. Recent progress in the field of single cell biology and transcriptomics has enabled unprecedented resolution of cell types, including delineation of previously unrecognized types and subtypes in the mammalian brain.

Josh Huang, Jonathan Ting, and Andreas Tolias will explore how cutting-edge and highly integrative experimental approaches are being leveraged for multi-feature analysis at the single cell level. Speakers will also address how these datasets support cell type classification efforts, increasingly precise tool development, and the functional dissection of mouse and human brain cell types. A short Q&A will follow presentations.

Josh Huang, PhD
Cold Spring Harbor Laboratory

Josh Huang is an investigator and the Charles and Marie Robertson Professor of Neuroscience at the Cold Spring Harbor Laboratory. His research focuses on the organization, development, and function of neural circuits in the cerebral cortex. Huang earned his PhD in molecular biology from Brandeis University and completed his postdoctoral training at Massachusetts Institute of Technology (MIT).

Jonathan T. Ting, PhD
Allen Institute for Brain Science

Jonathan T. Ting is an assistant investigator in the Human Cell Types group at the Allen Institute for Brain Science. His current work is focused on systematically exploring the diverse cell types of the human neocortex using an integrated electrophysiological, morphological, and molecular profiling approach. He earned his BS in biological sciences from the University of California at Davis, PhD in neurobiology and behavior from the University of Washington, and completed his postdoctoral training in the laboratory of Guoping Feng at the McGovern Institute for Brain Research at Massachusetts Institute of Technology (MIT) and Duke University Medical Center.

Andreas Tolias, PhD
Baylor College of Medicine

Andreas Tolias is an associate professor in the department of neuroscience at Baylor College of Medicine and the department of electrical and computer engineering at Rice University. He is also the founder and director of the Center for Neuroscience and Artificial Intelligence. Tolias is a Brown Foundation Endowed Chair of Neuroscience. He earned his BA and MA in natural sciences from Cambridge University, PhD in neuroscience at Massachusetts Institute of Technology (MIT), and completed his postdoctoral fellowship at the Max Planck Institute.

Session 5: Single Cell RNA Sequencing Reveals Dynamic Developmental Trajectories During Mammalian Brain Development

大脑发育，单细胞。

The development of the nervous system is a complex and branched dynamical process. These features pose important challenges to determining how the vast heterogeneity of the nervous system arises. Single cell RNA sequencing (RNA Seq) technologies offer an important tool to study developmental processes. However, analysis of these data are further complicated by the superposition of several sources of biological variability, including differentiation, maturation, and regional diversity. Early-stage investigators will highlight possibilities unlocked by single cell RNA sequencing techniques and technical challenges that remain.

Alex Pollen and Tom Nowakowski will present different strategies adopted to address sources of variation and complexity, including by using a comprehensive single cell survey of the developing human brain across five years, 48 individuals, and multiple stages of development and brain regions. Giorgia Quadrato will address the potential and limitations of modeling human disease progression and developmental trajectory using human organoids, and describe how single cell RNA sequencing can be used to asses organoids heterogeneity and similarity to their in vivo counterparts. Gioele La Manno will present a new method of “RNA velocity,” that can be used to study nervous system development and other dynamical processes. They will also highlight how this approach can be extended to obtain lineage tracing-like data from human embryonic tissue specimens. A panel discussion and Q&A will follow presentations.

Alex Pollen, PhD - University of California, San Francisco

Alex Pollen is an assistant professor of neurology at the University of California, San Francisco (UCSF). The Pollen lab studies human brain development from a genetic and evolutionary perspective using tools from single cell genomics and stem cell biology. Pollen earned his BA in biology from Harvard University, Ph.D. in neuroscience from Stanford University, an completed his postdoctoral training on cortical development with Arnold Kriegstein at UCSF.

Tom Nowakowski, PhD - University of California, San Francisco

Tom Nowakowski is an assistant professor at University of California, San Francisco (UCSF). Nowakowski earned his PhD from the University of Edinburgh and completed his postdoctoral training in the laboratory of Arnold Kriegstein at UCSF in 2017 where he pioneered the use of single cell RNA sequencing to study the heterogeneity of cellular populations in the developing brain and discovered the biomarkers of outer radial glia.

Giorgia Quadrato, PhD - University of Southern California

hPSC，口音有点重。

Giorgia Quadrato is an assistant professor in the Broad CIRM Center and Department of Stem Cell Biology and Regenerative Medicine at the University of Southern California (USC). She previously worked as a research associate in the Arlotta Laboratory at Harvard University and the Broad Institute of Massachusetts Institute of Technology and Harvard University. Quadrato's research focuses on modeling and investigating the molecular underpinnings behind human brain development and disease using 3D brain organoids derived from human pluripotent stem cells. Giorgia earned her BS, MS, and PhD in pharmacogenomic biotechnology from the University of Milano-Bicocca (Italy). She completed her postdoctoral training at the Hertie Institute for Clinical Brain Research in the Laboratory of Neuroregeneration and Repair, Tübingen Germany, where she investigated signaling pathways regulating adult neurogenesis and CNS axonal regeneration.

Gioele La Manno - Karolinska Instituet

老熟人了，早就细读过他的Cell的中脑文章了。统计功底比较强，但是看起来有点太artificial了。

Gioele La Manno is a member of Linnarsson Lab at Karolinska Instituet and is currently preparing to defend his PhD thesis. His work has focused on harnessing the wealth of information provided by single cell RNA sequencing to better understand brain development. In particular, he has been using machine learning and differential equation modelling to describe the sequence of states that neural progenitor cells undergo during their differentiation towards mature neurons. He earned his BS in biotechnology at University of Palermo and his MS in biomedicine at Karolinska Institutet.

Session 6: Reconstructing Brain Evolution with Single Cell RNA Sequencing Data

The stunning complexity of the brain is the result of evolutionary processes. Changes of brain size or connectivity are not sufficient to explain the diversity of vertebrate brains. Neuron types also change over evolutionary time, but elucidating their evolution has been challenging. Single cell and single nucleus RNA sequencing enable comparisons of neural cell types across species in an unbiased and quantitative way.

Trygve Bakken will describe the extent to which transcriptomic cell types are conserved in mouse and human cortex. Maria Antonietta Tosches will present how the comparison of reptilian and mammalian single cell RNA sequencing data inform us on the evolution of the cerebral cortex. A short Q&A will follow presentations.

Trygve Bakken, MD, PhD
Allen Institute for Brain Science

Trygve Bakken is a scientist at the Allen Institute for Brain Science and is helping build a quantitative census of cell types in the human brain. He builds computational tools to characterize the transcriptomic diversity of cell types with the aim to understand cell type evolution and role in neuropsychiatric disease. He earned his BA from Yale University, MS in physics and philosophy from the London School of Economics, and PhD in neuroscience and MD from the University of California, San Diego.

Maria Antonietta Tosches, PhD
Max Planck Institute for Brain Research

Maria Antonietta Tosches is a postdoc at the Max Planck Institute for Brain Research in Frankfurt, Germany. Her research focuses on the evolution of cell types and neural circuits in the vertebrate brain. She recently addressed the evolution of the cerebral cortex by applying single-cell genomics approaches to reptiles. Tosches studied biology in Pisa, Italy, and earned her PhD from the European Molecular Biology Laboratory in Heidelberg.