Team

Staff Profiles

Ed Lein, Ph.D.

Investigator

Ed Lein is an investigator at the Allen Institute for Brain Science and an Affiliate Professor in the Department of Neurological Surgery at the University of Washington. He received a B.S. in biochemistry from Purdue University and a Ph.D. in neurobiology from UC Berkeley, and performed postdoctoral work at the Salk Institute for Biological Studies. He joined the Allen Institute in 2004 and has provided scientific guidance for the creation of large-scale gene expression atlases of the adult and developing mammalian brain as catalytic community resources, including the inaugural Allen Mouse Brain Atlas and a range of developmental and adult human and non-human primate brain atlases. Particular interests of Dr. Lein include using the transcriptome as a core phenotype to understand brain organization at the regional, cellular and functional level, to understand what is unique about human brain, and to understand what is disrupted in brain diseases.  He now co-leads the Cell Types program and directs the Human Cell Types department, which aim to create a comprehensive understanding of human cortical cell types and circuits and what is specialized in human cortex, using quantitative single cell transcriptomic, anatomical and functional methods. Lein is also an Affiliate Professor in the Department of Neurological Surgery at the University of Washington.

Research

Research Interests

Research Interests I have been involved from the ground level in three major atlasing projects at the Allen Institute, originally as part of the team that generated the inaugural Allen Mouse Brain Atlas. Subsequently I led the production of the BrainSpan Atlas of the Developing Human Brain, a consortium-based effort to profile the transcriptome of the pre- and postnatal developing human brain, and the NIH Blueprint Non-Human Primate Atlas, which aims to carefully profile spatiotemporal gene expression patterning in the pre- and postnatal rhesus monkey forebrain. I am now spearheading the human cell types project, which aims to build upon these foundational gene expression studies in human brain by developing and implementing methods for the quantitative phenotypic analysis of individual cells of the human neocortex. A major focus of my research is using high-resolution anatomical transcriptome data to understand the molecular and cellular architecture of the mammalian neocortex and hippocampus. What is the molecular logic underlying cortical structure and function? What are the developmental mechanisms that direct the specification and maturation of cortical cell types, and is it possible to derive a transcription factor code that drives the cellular decision tree underlying progressive precursor fate restriction and specification of specific cortical neuron types? What is unique about human molecular and cellular cortical architecture, and the developmental dynamics that give rise to the massive expansion of the human neocortex? The human cell types project aims to study the fine structure of the human neocortex through the quantitative molecular, anatomical and functional analysis of single cells in postmortem and living neurosurgery-derived cortical tissues. Combining systematic data generation and advanced machine learning techniques, major goals are to derive a quantitative classification of human cortical cell types and to understand functional population dynamics in the living human neocortex. What are the unique genetic, structural and functional characteristics of the human neocortex that enable our great cognitive capabilities and could be specifically affected in neurological or neuropsychiatric diseases? What is different about cellular properties and functional circuit organization of the human neocortex compared to the dominant genetic model system for biomedical research, the mouse? By developing tools and techniques for the reliable preservation and cellular and circuit interrogation of human cortical tissues the project aims to broadly catalyze research on the human brain.

Expertise

  • Developmental neurobiology
  • Structural and cellular neuroanatomy
  • Transcriptomics

Research Programs

  • Cell types
  • Neural coding
  • Atlasing

Selected Publications View on PUBMED

Conserved cell types with divergent features in human versus mouse cortex

Nature
August 21, 2019

Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, Close JL, Long B, Johansen N, Penn O, Yao Z, Eggermont J, Höllt T, Levi BP, Shehata SI, Aevermann B, Beller A, Bertagnolli D, Brouner K, Casper T, Cobbs C, Dalley R, Dee N, Ding SL, Ellenbogen RG, Fong O, Garren E, Goldy J, Gwinn RP, Hirschstein D, Keene CD, Keshk M, Ko AL, Lathia K, Mahfouz A, Maltzer Z, McGraw M, Nguyen TN, Nyhus J, Ojemann JG, Oldre A, Parry S, Reynolds S, Rimorin C, Shapovalova NV, Somasundaram S, Szafer A, Thomsen ER, Tieu M, Quon G, Scheuermann RH, Yuste R, Sunkin SM, Lelieveldt B, Feng D, Ng L, Bernard A, Hawrylycz M, Phillips JW, Tasic B, Zeng H, Jones AR, Koch C, Lein ES

Classification of electrophysiological and morphological neuron types in mouse visual cortex

Nature Neuroscience
June 17, 2019

Gouwens NW, Sorensen SA, Berg J, Lee C, Jarsky T, Ting J, Sunkin S, Feng D, Anastassiou C, Barkan E, Bickley K, Blesie N, Braun T, Brouner K, Budzillo A, Caldejon S, Casper T, Castelli D, Chong P, Crichton K, Cuhaciyan C, Daigle T, Dalley R, Dee N, Desta T, Dingman S, Doperalski A, Dotson N, Egdorf T, Fisher M, de Frates RA, Garren E, Garwood M, Gary A, Gaudreault N, Godfrey K, Gorham M, Gu H, Habel C, Hadley K, Harrington J, Harris J, Henry A, Hill D, Josephsen S, Kebede S, Kim L, Kroll M, Lee B, Lemon T, Liu X, Long B, Mann R, McGraw M, Mihalas S, Mukora A, Murphy GJ, Ng L, Ngo K, Nguyen TN, Nicovich PR, Oldre A, Park D, Parry S, Perkins J, Potekhina L, Reid D, Robertson M, Sandman D, Schroedter M, Slaughterbeck C, Soler-Llavina C, Sulc J, Szafer A, Tasic B, Taskin N, Teeter C, Thatra N, Tung H, Wakeman W, Williams G, Young R, Zhou Z, Farrell C, Peng H, Hawrylycz MJ, Lein E, Ng L, Arkhipov A, Bernard A, Phillips J, Zeng H, Koch C

Epigenetic landscape and AAV targeting of human neocortical cell classes

bioRxiv
February 19, 2019

Mich JK, Hess EE, Graybuck LT, Somasundaram S, Miller JA, Ding Y, Shapovalova NV, Fong O, Yao S, Mortrud M, Chong P, Bertagnolli D, Goldy J, Casper T, Kroll M, Hodge RD, Bakken TE, Yao Z, Dee N, Cetin A, Smith KA, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Keene CD, Silbergeld DL, Gradinaru V, Sunkin SM, Zeng H, Lein ES, Tasic B, Ting JT, Levi BP

Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex

bioRxiv
January 13, 2019

Smith SJ, Sumbul U, Graybuck LT, Collman F, Sharmishtaa S, Gala R, Gliko O, Elabbady L, Miller J, Bakken T, Yao Z, Lein ES, Zeng H, Tasic B, Hawrylycz M

Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex

eLife
September 26, 2018

Seeman SC, Campagnola L, Davoudian PA, Hoggarth A, Hage TA, Bosma-Moody A, Baker CA, Lee, JH, Mihalas S, Teeter C, Ko AL, Ojemann JG, Gwinn RP, Silbergeld DL, Cobbs C, Phillips J, Lein E, Murphy G, Koch C, Zeng H, Jarsky T

Distinctive Structural and Molecular Features of Myelinated Inhibitory Axons in Human Neocortex

eNeuro
September 19, 2018

Micheva KD, Chang EF, Nana AL, Seeley WW, Ting JT, Cobbs C, Lein E, Smith SJ, Weinberg RJ, Madison DV

Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type

Nature Neuroscience
August 27, 2018

Boldog E, Bakken TE, Hodge RD, Novotny M, Aevermann BD, Baka J, Bordé S, Jennie L. Close, Diez-Fuertes F, Ding SL, Faragó N, Kocsis AK, Kovács B, Maltzer Z, McCorrison JM, Miller JA, Molnár G, Oláh G, Ozsvár A, Rózsa M, Shehata SI, Smith KA, Sunkin SM, Tran DN, Venepally P, Wall A, Puskás LG, Barzó P, Steemers FJ, Schork NJ, Scheuermann RH, Lasken RS, Lein ES, Tamás G

A robust ex vivo experimental platform for molecular-genetic dissection of adult human neocortical cell types and circuits

Scientific Reports
May 30, 2018

Ting JT, Kalmbach B, Chong P, de Frates R, Keene CD, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Ellenbogen RG, Koch C, Lein E

Genetic identification of brain cell types underlying schizophrenia

Nature Genetics
May 21, 2018

Skene NG, Bryois J, Bakken TE, Breen G, Crowley JJ, Gaspar HA, Giusti-Rodriguez P, Hodge RD, Miller JA, Muñoz-Manchado A, O'Donovan MC, Owen MJ, Pardiñas AF, Ryge J, Walters JTR, Linnarsson S, Lein ES, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sullivan PS, Hjerling-Leffler J

An anatomic transcriptional atlas of human glioblastoma

Science
May 11, 2018

Puchalski RB, Shah N, Miller J, Dalley R, Nomura SR, Yoon JG, Smith KA, Lankerovich M, Bertagnolli D, Bickley K, Boe AF, Brouner K, Butler S, Caldejon S, Chapin M, Datta S, Dee N, Desta T, Dolbeare T, Dotson N, Ebbert A, Feng D, Feng X, Fisher M, Gee G, Goldy J, Gourley L, Gregor BW, Gu G, Hejazinia N, Hohmann J, Hothi P, Howard R, Joines K, Kriedberg A, Kuan L, Lau C, Lee F, Lee H, Lemon T, Long F, Mastan N, Mott E, Murthy C, Ngo K, Olson E, Reding M, Riley Z, Rosen D, Sandman D, Shapovalova N, Slaughterbeck CR, Sodt A, Stockdale G, Szafer A, Wakeman W, Wohnoutka PE, White SJ, Marsh D, Rostomily RC, Ng L, Dang C, Jones A, Keogh B, Gittleman HR, Barnholtz-Sloan JS, Cimino PJ, Uppin MS, Keene CD, Farrokhi FR, Lathia JD, Berens ME, Iavarone A, Amy Bernard A, Lein E, Phillips JW, Rostad SW, Cobbs C, Hawrylycz MJ, Foltz GD

Cell type discovery using single-cell transcriptomics: implications for ontological representation

Human Molecular Genetics
May 1, 2018

Aevermann BD, Novotny M, Bakken T, Miller JA, Diehl AD, Osumi-Sutherland D, Lasken RS, Lein ES, Scheuermann RH

Single-nucleus and single-cell transcriptomes compared in matched cortical cell types

PLoS One
December 26, 2018

Bakken TE, Hodge RD, Miller JA, Yao Z, Nguyen TN, Aevermann B, Barkan E, Bertagnolli D, Casper T, Dee N, Garren E, Goldy J, Graybuck LT, Kroll M, Lasken RS, Lathia K, Parry S, Rimorin C, Scheuermann RH, Schork NJ, Shehata SI, Tieu M, Phillips JW, Bernard A, Smith KA, Zeng H, Lein ES, Tasic B

Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity

Nature Genetics
December 17, 2018

Coe BP, Stessman HAF, Sulovari A, Geisheker MR, Bakken TE, Lake AM, Dougherty JD, Lein ES, Hormozdiari F, Bernier RA, Eichler EE

Joint registration and synthesis using a probabilistic model for alignment of MRI and histological sections

Medical Image Analysis
December 1, 2018

Iglesias JE, Modat M, Peter L, Stevens A, Annunziata R, Vercauteren T, Lein E, Fischl B, Ourselin S

h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex

Neuron
November 1, 2018

Kalmbach BE, Buchin A, Long B, Close J, Nandi A, Miller JA, Bakken TE, Hodge RD, Chong P, de Frates R, Dai K, Maltzer Z, Nicovich PR, Keene CD, Silbergeld DL, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Koch C, Anastassiou CA, Lein ES, Ting JT

Shared and distinct transcriptomic cell types across neocortical areas

Nature
October 31, 2018

Tasic B, Yao Z, Graybuck LT, Smith KA, Nguyen TN, Bertagnolli D, Goldy J, Garren E, Economo MN, Viswanathan S, Penn O, Bakken T, Menon V, Miller J, Fong O, Hirokawa KE, Lathia K, Rimorin C, Tieu M, Larsen R, Casper T, Barkan E, Kroll M, Parry S, Shapovalova NV, Hirschstein D, Pendergraft J, Sullivan HA, Kim TK, Szafer A, Dee N, Groblewski P, Wickersham I, Cetin A, Harris JA, Levi BP, Sunkin SM, Madisen L, Daigle TL, Looger L, Bernard A, Phillips J, Lein E, Hawrylycz M, Svoboda K, Jones AR, Koch C, Zeng H

Comprehensive cellular-resolution atlas of the adult human brain

Journal of Comparative Neurology
July 15, 2016

Ding SL, Royall JJ, Sunkin SM, Ng L, Facer BA, Lesnar P, Guillozet-Bongaarts A, McMurray B, Szafer A, Dolbeare TA, Stevens A, Tirrell L, Benner T, Caldejon S, Dalley RA, Dee N, Lau C, Nyhus J, Reding M, Riley ZL, Sandman D, Shen E, van der Kouwe A, Varjabedian A, Write M, Zollei L, Dang C, Knowles JA, Koch C, Phillips JW, Sestan N, Wohnoutka P, Zielke HR, Hohmann JG, Jones AR, Bernard A, Hawrylycz MJ, Hof PR, Fischl B, Lein ES

A comprehensive transcriptional map of primate brain development

Nature
July 13, 2016

Bakken TE, Miller JA, Ding SL, Sunkin SM, Smith KA, Ng L, Szafer A, Dalley RA, Royall JJ, Lemon T, Shapouri S, Aiona K, Arnold J, Bennett JL, Bertagnolli D, Bickley K, Boe A, Brouner K, Butler S, Byrnes E, Caldejon S, Carey A, Cate S, Chapin M, Chen J, Dee N, Desta T, Dolbeare TA, Dotson N, Ebbert A, Fulfs E, Gee G, Gilbert TL, Goldy J, Gourley L, Gregor B, Gu G, Hall J, Haradon Z, Haynor DR, Hejazinia N, Hoerder-Suabedissen A, Howard R, Jochim J, Kinnunen M, Kriedberg A, Kuan CL, Lau C, Lee CK, Lee F, Luong L, Mastan N, May R, Melchor J, Mosqueda N, Mott E, Ngo K, Nyhus J, Oldre A, Olson E, P

Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons

Nature Protocols
March 2016

Krishnaswami SR, Grindberg RV, Novotny M, Venepally P, Lacar B, Bhutani K, Linker SB, Pham S, Erwin JA, Miller JA, Hodge R, McCarthy JK, Kelder M, McCorrison J, Aevermann BD, Fuertes FD, Scheuermann RH, Lee J, Lein ES, Schork N, McConnell MJ, Gage FH, Lasken RS

Canonical genetic signatures of the adult human brain

Nature Neuroscience
December 2015

Hawrylycz M, Miller JA, Menon V, Feng D, Dolbeare T, Guillozet-Bongaarts AL, Jegga AG, Aronow BJ, Lee CK, Bernard A, Glasser MF, Dierker DL, Menche J, Szafer A, Collman F, Grange P, Berman KA, Mihalas S, Yao Z, Stewart L, Barabási AL, Schulkin J, Phillips J, Ng L, Dang C, Haynor DR, Jones A, Van Essen DC, Koch C, Lein E

Transcriptional landscape of the prenatal human brain

Nature
April 2, 2014

Miller JA, Ding SL, Sunkin SM, Smith KA, Ng L, Szafer A, Ebbert A, Riley ZL, Royall JJ, Aiona K, Arnold JM, Bennet C, Bertagnolli D, Brouner K, Butler S, Caldejon S, Carey A, Cuhaciyan C, Dalley RA, Dee N, Dolbeare TA, Facer BA, Feng D, Fliss TP, Gee G, Goldy J, Gourley L, Gregor BW, Gu G, Howard RE, Jochim JM, Kuan CL, Lau C, Lee CK, Lee F, Lemon TA, Lesnar P, McMurray B, Mastan N, Mosqueda N, Naluai-Cecchini T, Ngo NK, Nyhus J, Oldre A, Olson E, Parente J, Parker PD, Parry SE, Stevens A, Pletikos M, Reding M, Roll K, Sandman D, Sarreal M, Shapouri S, Shapovalova NV, Shen EH, Sjoquist N, Slau

Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity

Cerebral Cortex
September 7, 2013

Sorensen SA, Bernard A, Menon V, Royall JJ, Glattfelder KJ, Hirokawa K, Mortrud M, Miller JA, Zeng H, Hohmann JG, Jones AR, Lein ES

Transcriptional architecture of the primate neocortex

Neuron
March 22, 2012

Bernard A, Lubbers LS, Tanis KQ, Luo R, Podtelezhnikov AA, Finney EM, McWhorter MME, Serikawa K, Lemon T, Morgan R, Copeland C, Smith K, Cullen V, Davis-Turak J, Lee CK, Sunkin SM, Loboda AP, Levine DM, Stone DJ, Hawrylycz MJ, Roberts CJ, Jones AR, Geschwind DH, Lein ES

An anatomically comprehensive atlas of the adult human brain transcriptome

Nature
December 2012

Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, Daly BD, Dang C, Datta S, Dee N, Dolbeare T, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeria PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sun

Genomic anatomy of the hippocampus

Neuron
December 26, 2008

Thompson CL, Pathak SD, Jeromin A, Ng LL, MacPherson CR, Mortrud MT, Cusick A, Riley ZL, Sunkin SM, Bernard A, Puchalski RB, Gage FH, Jones AR, Bajic VB, Hawrylycz MJ, Lein ES

Genome-wide atlas of gene expression in the adult mouse brain

Nature
January 11, 2007

Lein ES, Hawrylycz M, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang C, Datta S, Dee NR, Desaki AL, Deta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Mich