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
Single-cell transcriptomic evidence for dense intracortical neuropeptide networks.
eLife
November 11, 2019
Smith SJ, Sümbül U, Graybuck LT, Collman F, Seshamani S, Gala R, Gliko O, Elabbady L, Miller JA, Bakken TE, Rossier J, Yao Z, Lein E, 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
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
Medical Image Analysis
December 1, 2018
Iglesias JE, Modat M, Peter L, Stevens A, Annunziata R, Vercauteren T, Lein E, Fischl B, Ourselin S
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