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Fredrik Lanner

Assistant professor

Postal address : Department of Clinical Science, Intervention and Technology (CLINTEC), H9, x, Karolinska Universitetssjukhuset, K 57 141 86 Stockholm, Sweden

Research description

Pluripotency, Embryonic Stem Cells and Regenerative Medicine

The Lanner lab aims to:

1. Uncover the fundamental principles underlying how the first cell types and pluripotency is established in the early human embryo.

2. Establish a good manufacturing practice (GMP) bank of clinically compliant high quality embryonic stem cells (ESCs).

3. Explore treatment of age-related macula degeneration using ESC derived retinal pigmented epithelial cells.

ESCs isolated from the human blastocyst can be propagated indefinitely and directed into any cell type of the adult human, offering great potential for regenerative medicine to replace lost or damaged tissues. The knowledge of how these pluripotent cells are established and controlled in vivo is generated primarily in animal modes such as the mouse while our knowledge of the same process in the human is rudimentary and key differences are emerging. We will explore these issues through single cell mRNA sequencing, pioneering genetic technologies and functional assays in human blastocysts. This fundamental knowledge will also be important for our understanding of infertility, a problem affecting 10-15% of all couples in our society.

We have established an efficient differentiation methodology of ESCs into clinically relevant cell types. However, before these safely can become clinical practice, additional hurdles must be overcome such as GMP production and immune matching of cells and patients. By establishing the KI Stem Cell Bank we hope to resolve these issues and facilitate efforts to move stem cell based regenerative medicine into the clinic. Finally, we will specifically aim to initiate trials based on ESC in treatment of macular degeneration, the major cause of blindness in our elderly population.

 

Current Lab members

Dr. Liselotte Antonsson, Lab manager, Establishing clinically compliant embryonic stem cells

Mona Hedenskog, Lab technician, Establishing clinically compliant embryonic stem cells

Dr. Sebastian Hildebrand, Postdoc. Establishing the biophysical properties of the trofectoderm, the first epithelial celltype.

Dr. Sarita Pauliina Panula, Postdoc. Establishing novel tools to explore distinct stem cell types in the human embryo.

Dr. Siqin Wu, Industrial Postdoc (Spiber Technologies). Developing novel ESCs differentiation strategies using spider silk.

Dr. Pankaj Kumar, Postdoc. Bioinformatics of pluripotency and early human development.

Dr. Nicolas Ortega, Postdoc. Gene editing in early bovine and human embryos.

John Paul Schell, PhD student. Dissecting naive and primed pluripotency.

Alvaro Plaza Reyes, PhD student. Treating AMD using ESCs. Establishing genetic technologies to study early human development. 

Sara Padrell Sánchez, PhD student. Treating AMD using ESCs.

Sandra Petrus-Reurer, PhD student in Kvanta Lab, co-supervised. Treating AMD using ESCs.

Leni Wagner, PhD student in Damdimopoulou Lab, co-supervised. Stem cells of the adult ovary.

Nerges Winblad, Research assistant. Establishing genetic technologies to study early human development.

Past Lab members

Dr. Sophie Petroploulos, Postdoc. Single cell RNA sequencing analysis of human blastocyst formation. 

Interested in joining the lab?
Applications for post-doc positions are very welcomed if the applicant can bring financing. Otherwise early contacts are encouraged to plan applications for external personal post-doc grants.

 

KI Stem Cell Bank

Together with Liselotte Antonsson and Mona Hedenskog we are working intensively to derive clinically compliant GMP ESCs which we will be usefull for academic and industial efforts within stem cell based regenerative medicin. 

 

Publications

The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching

Sebastian Hildebrand, Sara Hultin,Aravindh Subramani, Sophie Petropoulos, Yuanyuan Zhang, Xiaofang Cao, John Mpindi, Olli Kalloniemi, Staffan Johansson, Arindam Majumdar, Fredrik Lanner & Lars Holmgren. Scientific Reports 2017

At the heart of gene edits in human embryo

Winblad N., and Lanner F, Nature 2017

Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells 

Authors Nosi U, Lanner F, Huang T, Cox B. Cell Reports 2017

 

Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States.

Collier AJ, Panula SP, Schell JP, Chovanec P, Plaza Reyes A, Petropoulos S, Corcoran AE, Walker R, Douagi I, Lanner F, Rugg-Gunn PJ. Cell Stem Cell. 2017

 

Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy.

Petrus-Reurer S, Bartuma H, Aronsson M, Westman S, Lanner F, André H, Kvanta A. Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):1314-1322. doi: 10.1167/iovs.16-20738.

 

Position- and Hippo signaling-dependent plasticityduring lineage segregation in the early mouse embryo.

Posfai E, Petropoulos S, de Barros FR, Schell JP, Jurisica I, Sandberg R, Lanner F, Rossant J. Elife. 2017 Feb 22;6. pii: e22906. doi: 10.7554/eLife.22906.

 

Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos

Plaza Reyes A. and Lanner F. Development  2017  144: 3-7;  doi: 10.1242/dev.139683

 

Single-cell sequencing of the small-RNA transcriptome

Faridani OR, Abdullayev I, Hagemann-Jensen M, Schell JP, Lanner F, Sandberg R. Nat Biotechnol. 2016 Oct 31. doi: 10.1038/nbt.3701.

 

Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation.

Chen G, Schell JP, Benitez JA, Petropoulos S, Yilmaz M, Reinius B, Alekseenko Z, Shi L, Hedlund E, Lanner F, Sandberg R, Deng Q.

Genome Res. 2016 Aug 2. pii: gr.201954.115. [Epub ahead of print]

 

Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos.

Madissoon E, Jouhilahti EM, Vesterlund L, Töhönen V, Krjutškov K, Petropoulous S, Einarsdottir E, Linnarsson S, Lanner F, Månsson R, Hovatta O, Bürglin TR, Katayama S, Kere J.

Sci Rep. 2016 Jul 14;6:28995. doi: 10.1038/srep28995.

 

Single-cell RNA-seq reveals lineage and X-chromosome dynamics in human preimplantation embryos
Sophie Petropoulos, Daniel Edsgärd, Björn Reinius, Qiaolin Deng, Sarita Pauliina Panula, Simone Codeluppi, Alvaro Plaza Reyes, Sten Linnarsson, Rickard Sandberg, Fredrik Lanner
Cell, published online 7 April 2016, doi: 10.1016/j.cell.2016.03.023

 

Single-cell RNA sequencing: revealing human pre-implantation development, pluripotency and germline development.

Petropoulos S, Panula SP, Schell JP, Lanner F.

J Intern Med. 2016 Apr 5. doi: 10.1111/joim.12493.

 

Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model.

Alvaro Plaza Reyes, Sandra Petrus-Reurer, Liselotte Antonsson, Sonya Stenfelt, Hammurabi Bartuma, Sarita Panula, Theresa Mader, Iyadh Douagi, Helder André, Outi Hovatta, Fredrik Lanner, Anders Kvanta. 

Stem Cell Reports, online 24 december 2015

 

Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells.

Zhang H, Panula S, Petropoulos S, Edsgärd D, Busayavalasa K, Liu L, Li X, Risal S, Shen Y, Shao J, Liu M, Li S, Zhang D, Zhang X, Gerner RR, Sheikhi M, Damdimopoulou P, Sandberg R, Douagi I, Gustafsson JÅ, Liu L, Lanner F, Hovatta O, Liu K.

Nat Med. 2015 Oct 7;21(10):1116-8

 

Lineage specification in the early mouse embryo.

Lanner F.

Exp Cell Res. 2014 Feb 1;321(1):32-9. doi: 10.1016/j.yexcr.2013.12.004

 

Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate.

Findlay GM, Smith MJ, Lanner F, Hsiung MS, Gish GD, Petsalaki E, Cockburn K, Kaneko T, Huang H, Bagshaw RD, Ketela T, Tucholska M, Taylor L, Bowtell DD, Moffat J, Ikura M, Li SS, Sidhu SS, Rossant J, Pawson T.

Cell. 2013 Feb 28;152(5):1008-20. doi: 10.1016/j.cell.2013.01.056.

 

Cell-surface proteomics identifies lineage-specific markers of embryo-derived stem cells.

Rugg-Gunn PJ, Cox BJ, Lanner F, Sharma P, Ignatchenko V, McDonald AC, Garner J, Gramolini AO, Rossant J, Kislinger T.

Dev Cell. 2012 Apr 17;22(4):887-901. doi: 10.1016/j.devcel.2012.01.005.

 

The role of FGF/Erk signaling in pluripotent cells.

Lanner F, Rossant J.

Development. 2010 Oct;137(20):3351-60. doi: 10.1242/dev.050146.

 

FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst.

Yamanaka Y, Lanner F, Rossant J.

Development. 2010 Mar;137(5):715-24. doi: 10.1242/dev.043471.

Academic honours, awards and prizes

Swedish Research Council 

Vetenskapsrådet startsida

  

 

 

 

 

Swedish Foundation for Strategic Research

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Ragnar Söderberg Foundation

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Mats Sundin Fellowship

 

ÅKE WIBERGS STIFTELSE

 

 

 

Research Associate position, funded by the Board of Research, Karolinska Institutet

 

CIMED

 

 

 

Knut och Alice Wallenbergs Stiftelse

Knut och Alice Wallenbergs Stiftelse - Stödjer vetenskaplig forskning och infrastruktur inom naturvetenskap, teknik och medicin

Publications

Biotechnology: At the heart of gene edits in human embryos
Winblad N, Lanner F
Nature 2017;548(7668):398-400

Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States
Collier Aj, Panula Sp, Schell Jp, Chovanec P, Plaza Reyes A, Petropoulos S, et al
Cell stem cell 2017;20(6):874-890.e7

Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy
Petrus-reurer S, Bartuma H, Aronsson M, Westman S, Lanner F, André H, et al
Investigative ophthalmology & visual science 2017;58(2):1314-1322

Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells
Nosi U, Lanner F, Huang T, Cox B
Cell reports 2017;19(6):1101-1109

Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo
Posfai E, Petropoulos S, De Barros Fro, Schell Jp, Jurisica I, Sandberg R, et al
eLife 2017;6():-

The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching
Hildebrand S, Hultin S, Subramani A, Petropoulos S, Zhang Y, Cao X, et al
Scientific reports 2017;7(1):9540-

Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos
Plaza Reyes A, Lanner F
Development (Cambridge, England) 2017;144(1):3-7

Adult Human and Mouse Ovaries Lack DDX4-Expressing Functional Oogonial Stem Cells EDITORIAL COMMENT
Zhang H, Panula S, Petropoulos S, Edsgard D, Busayavalasa K, Liu L, et al
OBSTETRICAL & GYNECOLOGICAL SURVEY 2016;71(1):29-30

Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos
Madissoon E, Jouhilahti Em, Vesterlund L, Töhönen V, Krjutškov K, Petropoulous S, et al
Scientific reports 2016;6():28995-

Corrigendum: Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos
Madissoon E, Jouhilahti Em, Vesterlund L, Töhönen V, Krjutškov K, Petropoulos S, et al
Scientific reports 2016;6():32053-

Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
Chen G, Schell Jp, Benitez Ja, Petropoulos S, Yilmaz M, Reinius B, et al
Genome research 2016;26(10):1342-1354

Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos
Petropoulos S, Edsgärd D, Reinius B, Deng Q, Panula Sp, Codeluppi S, et al
Cell 2016;167(1):285-

Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos
Petropoulos S, Edsgärd D, Reinius B, Deng Q, Panula Sp, Codeluppi S, et al
Cell 2016;165(4):1012-26

Single-cell RNA sequencing: revealing human pre-implantation development, pluripotency and germline development
Petropoulos S, Panula Sp, Schell Jp, Lanner F
Journal of internal medicine 2016;280(3):252-64

Single-cell sequencing of the small-RNA transcriptome
Faridani Or, Abdullayev I, Hagemann-jensen M, Schell Jp, Lanner F, Sandberg R
Nature biotechnology 2016;34(12):1264-1266

The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation
Jouhilahti Em, Madissoon E, Vesterlund L, Töhönen V, Krjutškov K, Plaza Reyes A, et al
Development (Cambridge, England) 2016;143(19):3459-3469

Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model
Plaza Reyes A, Petrus-reurer S, Antonsson L, Stenfelt S, Bartuma H, Panula S, et al
Stem cell reports 2016;6(1):9-17

Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells
Zhang H, Panula S, Petropoulos S, Edsgärd D, Busayavalasa K, Liu L, et al
Nature medicine 2015;21(10):1116-8

Lineage specification in the early mouse embryo
Lanner F
Experimental cell research 2014;321(1):32-9

Hypoxia-induced arterial differentiation requires adrenomedullin and notch signaling
Lanner F, Lee Kl, Ortega Gc, Sohl M, Li X, Jin S, et al
Stem cells and development 2013;22(9):1360-9

Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate
Findlay Gm, Smith Mj, Lanner F, Hsiung Ms, Gish Gd, Petsalaki E, et al
Cell 2013;152(5):1008-20

Location of transient ectodermal progenitor potential in mouse development
Li Ly, Liu C, Biechele S, Zhu Qq, Song L, Lanner F, et al
DEVELOPMENT 2013;140(22):4533-43

Porcn-dependent Wnt signaling is not required prior to mouse gastrulation
Biechele S, Cockburn K, Lanner F, Cox Bj, Rossant J
DEVELOPMENT 2013;140(14):2961-71

Cell-Surface Proteomics Identifies Lineage-Specific Markers of Embryo-Derived Stem Cells
Rugg-gunn Pj, Cox Bj, Lanner F, Sharma P, Ignatchenko V, Mcdonald Ach, et al
DEVELOPMENTAL CELL 2012;22(4):887-901

Constitutive heterochromatin reorganization during somatic cell reprogramming
Fussner E, Djuric U, Strauss M, Hotta A, Perez-iratxeta C, Lanner F, et al
EMBO JOURNAL 2011;30(9):1778-89

Numblike and Numb differentially affect p53 and Sonic Hedgehog signaling
Liu Ln, Lanner F, Lendahl U, Das D
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2011;413(3):426-31

Control of Notch-ligand endocytosis by ligand-receptor interaction
Hansson Em, Lanner F, Das D, Mutvei A, Marklund U, Ericson J, et al
JOURNAL OF CELL SCIENCE 2010;123(17):2931-42

FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst
Yamanaka Y, Lanner F, Rossant J
DEVELOPMENT 2010;137(5):715-24

Heparan Sulfation-Dependent Fibroblast Growth Factor Signaling Maintains Embryonic Stem Cells Primed for Differentiation in a Heterogeneous State
Lanner F, Lee Kl, Sohl M, Holmborn K, Yang H, Wilbertz J, et al
STEM CELLS 2010;28(2):191-200

Notch induces cyclin-D1-dependent proliferation during a specific temporal window of neural differentiation in ES cells
Das D, Lanner F, Main H, Andersson Er, Bergmann O, Sahlgren C, et al
DEVELOPMENTAL BIOLOGY 2010;348(2):153-66

Sp1 mediate hypoxia induced ephrinB2 expression via a hypoxia-inducible factor independent mechanism
Sohl M, Lanner F, Farnebo F
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2010;391(1):24-7

The role of FGF/Erk signaling in pluripotent cells
Lanner F, Rossant J
DEVELOPMENT 2010;137(20):3351-60

Characterization of the murine Ephrin-B2 promoter
Sohl M, Lanner F, Farnebo F
GENE 2009;437(1-2):54-9

Assessment of NORE1A as a putative tumor suppressor in human neuroblastoma
Geli J, Kogner P, Lanner F, Natalishvili N, Juhlin C, Kiss N, et al
INTERNATIONAL JOURNAL OF CANCER 2008;123(2):389-394

Notch signaling regulates platelet-derived growth factor receptor-beta expression in vascular smooth muscle cells
Jin S, Hansson Em, Tikka S, Lanner F, Sahlgren C, Farnebo F, et al
CIRCULATION RESEARCH 2008;102(12):1483-91

Functional arterial and venous fate is determined by graded VEGF signaling and notch status during embryonic stem cell differentiation
Lanner F, Sohl M, Farnebo F
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 2007;27(3):487-93

Lentiviral rescue of vascular endothelial growth factor receptor-2 expression in Flk1-/- embryonic stem cells shows early priming of endothelial precursors
Li Xj, Edholm D, Lanner F, Breier G, Farnebo F, Dimberg A, et al
STEM CELLS 2007;25(12):2987-95

The Ras effectors NORE1A and RASSF1A are frequently inactivated in pheochromocytoma and abdominal paraganglioma
Geli J, Kiss N, Lanner F, Foukakis T, Natalishvili N, Larsson O, et al
ENDOCRINE-RELATED CANCER 2007;14(1):125-34

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