The incredible complexity of the human brain poses enormous challenges in understanding how the brain underlies our thoughts and behaviors, and what goes wrong in disease. Furthermore, the inaccessibility of the human brain necessitates the use of closely related model organisms to understand many aspects of brain structure and function that cannot be studied in human. New highly scalable technologies for studying individual cells on the basis of the genes they use are rapidly accelerating the field to create complete maps of the types of cells that make up the brain. These methods also allow mapping of homologous cell types across species to understand what can be studied in model organisms and what is unique about the human brain. This webinar will present results from the BRAIN Initiative Cell Census Network (biccn.org) recently published in Science that describes the first draft of a brain-wide cell atlas of the adult human brain. Based on a single cell RNA sequencing (single cell transcriptomics), this effort describes the exceptional diversity of brain cell types and their distribution across the brain, identifying over 3000 cell types. These cell atlasing efforts have entered the next phase through the BRAIN Initiative Cell Atlas Network (BICAN) focused on human and closely related non-human primate model organisms. These new efforts use a combination of single cell transcriptomics, epigenomics and spatial transcriptomics to identify all cell types and map their spatial organization both in local tissue microarchitecture and the larger-scale microarchitecture of the brain. Finally, these cell atlases are created to be foundational community resources in the spirit of the Human Genome Project. Effective open access tools are essential to realize the potential of these resources to standardize and accelerate efforts across the field to understand brain function and disease. Tools to visualize these data and for users to map their own data against will be described. Speakers: 03:39 - Ed Lein, Senior Investigator at the Allen Institute for Brain Science: Introduction and Overview 15:20 - Kimberly Siletti - Assistant Professor at the University Medical Center Utrecht Title of talk: Transcriptomic cell-type diversity across the human brain Read “Transcriptomic diversity of cell types across the adult human brain” here: https://doi.org/10.1126/science.add7046 24:18 - Rebecca Hodge - Assistant Investigator at the Allen Institute for Brain science Title of talk: Building comprehensive cellular atlases of human and non-human primate brains using single cell genomics Read "Comparative transcriptomics reveals human-specific cortical features" here: https://www.science.org/doi/10.1126/science.ade9516 Read: Interindividual variation in human cortical cell type abundance and expression" here: https://www.science.org/doi/10.1126/science.adf2359 Read "Transcriptomic cytoarchitecture reveals principles of human neocortex organization" here: https://www.science.org/doi/10.1126/science.adf6812 32:28 - Stephanie Seeman - Scientist at the Allen Institute for Brain Science Read "Comparative transcriptomics reveals human-specific cortical features" here: https://www.science.org/doi/10.1126/science.ade9516 Read "Transcriptomic cytoarchitecture reveals principles of human neocortex organization" here: https://www.science.org/doi/10.1126/science.adf6812 41:30 - Elysha Fiabane - Product Manager at the Allen Institute for Brain Science Title of talk: Web Tools for Visualizing and Analyzing Human and Mammalian Brain Atlases Cell Types Knowledge Explorer https://knowledge.brain-map.org/celltypes ABC Atlas https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas MapMyCells http://knowledge.brain-map.org/mapmycells/process/ 41:30 - Q&A Moderator: Jimena Garcia - Program Manager, Inclusive Research at Allen Institute Read more about HMBA (Human and Mammalian Brain Atlas) efforts, including links to papers and datasets via: https://www.biccn.org/science/human-and-nhp-cell-atlas and https://www.portal.brain-bican.org/. We truly appreciate your engagement with this webinar and look forward to connecting with you again at future events, listed at brain-bican.org/events. This webinar has been supported by the BRAIN Initiative Cell Atlas Network (BICAN) of the National Institutes of Health under the Human and Mammalian Brain Atlas (HMBA) Consortium, award number UM1MH130981. The publications were supported by and coordinated through the BICCN (biccn.org) and BICAN (brain-bican.org).

The millions to billions of cells that comprise mammalian brains are organized into many highly specialized cell types. Previous studies have demonstrated that known and novel cell types can be identified by their single-cell gene expression profiles. However, the actual number of cell types in the brain and the degree of diversity among these cell types has been unknown. This webinar presents a new collection of studies from the BRAIN Initiative Cell Atlas Network (biccn.org) and published in Nature on Dec 14, 2023, that report the first complete cell type atlas of a mammalian brain, with over 30 million cells profiled from the adult mouse brain using a combination of single-cell transcriptomic, epigenomic, and spatial transcriptomic approaches, identifying over 5,300 cell types in the entire mouse brain. These studies uncover multitudes of organizing principles of the extraordinary cell type diversity across the brain. This collective body of work represents a landmark achievement that will have far-reaching impact on understanding cell type-based brain circuit function across the neuroscience field. More about the collection of studies, published in Nature on December 13, 2023: https://www.biccn.org/science/whole-mouse-brain Speakers: 1:21 Overview - Hongkui Zeng https://www.biccn.org/science/whole-mouse-brain 6:20 A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain - Zizhen Yao https://www.nature.com/articles/s41586-023-06812-z 17:38 Molecularly defined and spatially resolved cell atlas of whole mouse brain - Xingjie Pan https://www.nature.com/articles/s41586-023-06808-9 28:52 The molecular cytoarchitecture of the adult mouse brain - Jonah Langlieb https://www.nature.com/articles/s41586-023-06818-7 38:40 Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain - Hanqing Liu https://www.nature.com/articles/s41586-023-06805-y 51:59 Single-cell analysis of chromatin accessibility in adult mouse brain - Songpeng Zu https://www.nature.com/articles/s41586-023-06824-9 1:00:25 Brain-wide correspondence of neuronal epigenomics and distant projections - Jingtian Zhou https://www.nature.com/articles/s41586-023-06823-w 1:11:01 A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons - Carla Winter https://www.nature.com/articles/s41586-023-06817-8 1:22:10 Spatial atlas of the mouse central nervous system at molecular resolution - Hailing Shi https://www.nature.com/articles/s41586-023-06569-5 1:32:49 Conserved and divergent gene regulatory programs of the mammalian neocortex - Ethan Armand https://www.nature.com/articles/s41586-023-06819-6 1:43:34 Evolution of neuronal cell classes and types in the vertebrate retina - Karthik Shekhar https://www.nature.com/articles/s41586-023-06638-9 1:54:21 Q&A. Moderator: Yasmeen Hussain, Allen Institute for Brain Science --- The research and webinar presented was funded by grants from the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative (The BRAIN Initiative). The publications were supported by and coordinated through the BICCN (biccn.org) and BICAN (brain-bican.org).

The human brain contains more than 100 billion cells, but exactly how these cells are organized into types and how these cell types differ between brain regions and species is an open question. This webinar presents a new collection of studies focused on defining and characterizing the underlying gene expression, gene regulatory, and morphoelectric features of cell types in the human and non-human primate (NHP) brain. These studies employ a range of cellular resolution methods (most notably single cell genomics) for this purpose, marking the beginning of an exciting new era of high-resolution human and NHP analyses. The implications for understanding of human brain function, disease and disease modeling are profound. More about the collection of studies: https://www.biccn.org/science/human-and-nhp-cell-atlas Speakers: Ed Lein, Allen Institute for Brain Science​ 1:18 Kimberly Siletti, University Medical Center Utrecht, Netherlands​, 5:12 "Transcriptomic diversity of cell types in the adult human brain" http://www.science.org/doi/10.1126/science.add7046 Trygve Bakken, Allen Institute for Brain Science​, 13:45 "Comparative transcriptomics reveals human-specific cortical features" http://www.science.org/doi/10.1126/science.ade9516 Lijuan Liu, Southeast University, China​, 22:40 "Whole Human-Brain Mapping of Single Cortical Neurons for Profiling Morphological Diversity and Stereotypy" https://www.science.org/doi/10.1126/sciadv.adf3771 Wei Tian, Salk Institute​, 32:17 " Epigenomic complexity of the human brain revealed by single-cell DNA methylomes and 3D genome structures" http://www.science.org/doi/10.1126/science.adf5357 Chang Kim, University of California, San Francisco​, 41:42 "Spatiotemporal molecular dynamics of the developing human thalamus" http://www.science.org/doi/10.1126/science.adf9941 Q&A: 51:32 Moderator:​ Yasmeen Hussain, Allen Institute for Brain Science --- The research and webinar presented was funded by grants from the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative (The BRAIN Initiative). The publications were supported by and coordinated through the BICCN (biccn.org) and BICAN (brain-bican.org).

Learn about the Cell Types Knowledge Explorer (CTKE), a web tool that supports exploring individual cell types in M1. See the tool at https://knowledge.brain-map.org/celltypes.

The Brain Initiative Cell Census Network (BICCN) is a collaborative consortium of many labs interested in the cellular composition of the mammalian brain. BICCN has recently published a flagship publication describing the overall project, along with a companion package of papers describing the cell types, connectivity, anatomy and other properties of the mammalian primary motor cortex (MOp or M1). At this webinar, learn about this multimodal research from leaders of some of the research teams involved. Learn more: https://alleninstitute.org/what-we-do/brain-science/events-training/biccn-flagship-release To read Q&A and ask follow-up questions, please visit our forum: https://community.brain-map.org/t/decoding-the-mammalian-motor-cortex-biccn-flagship-release-webinar-q-a/1316