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Fredrik Lanner

Senior researcher

Email:

fredrik.lanner@ki.se

Department and organisational affiliation:

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). Our first clinically compliant stem cell line KARO1 is now available for collaborators in the stage of clinical translation.

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

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

Dr. Heather Main, BMA, Establishing GMP grade retinal cells from embryonic stem cells

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.

Dr. Paschalis Efstathopoulos, Postdoc. Generation of pancreatic tissues for treatment of diabetes

Dr. Sandra Petrus-Reurer, Postdoc also working in Anders Kvantas group. Treating AMD using ESCs.

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.

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.

Laura Baque Vidal, ERASMUS student

Past Lab members

Dr. Sophie Petroploulos, PI at KI and University of Montreal

Dr. Sebastian Hildebrand, Postdoc. Now working at Tecan

Dr. Liselotte Antonsson

Dr. Sarita Panula, Postdoc. Now working at Pricilla Therapeutics.

Nashwan Jalal Markus, now working at the productive Unit Karolinska Hospital

Haojiang Lu

Philipp Schenk

Angelos Gkikas

Nariman Gharari

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 Mona Hedenskog and Heather Main we are working intensively to derive clinically compliant ESCs which we will be usefull for academic and industial efforts within stem cell based regenerative medicin. Our first GMP grade line is derived, please contact us if interested in such cell line.

Publications

Single cell map of the human ovarian cortex

Wagner M, Yoshihara M, Dougai I, Damdimopoulos A, Panula S, Petropoulos S, Lu H, Pettersson K, Palm K, Katayama S, Hovatta O, Kere J, Lanner F, Damdimopoulou P. bioRxiv 2019

iFISH is a publically available resource enabling versatile DNA FISH to study genome architecture.

Gelali E, Girelli G, Matsumoto M, Wernersson E, Custodio J, Mota A, Schweitzer M, Ferenc K, Li X, Mirzazadeh R, Agostini F, Schell JP, Lanner F, Crosetto N, Bienko M.Nat Commun. 2019

Time Matters: Gene Editing at the Mouse 2-Cell Embryo Stage Boosts Knockin Efficiency.

Plaza Reyes A, Lanner F. Cell Stem Cell. 2018

Functional genetics of early human development.

Ortega NM, Winblad N, Plaza Reyes A, Lanner F. Curr Opin Genet Dev. 2018

Subretinal Transplantation of Human Embryonic Stem Cell Derived-retinal Pigment Epithelial Cells into a Large-eyed Model of Geographic Atrophy

Sandra Petrus-Reurer, Hammurabi Bartuma, Monica Aronsson, Sofie Westman, Fredrik Lanner, Anders Kvanta, JOVE 2018

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.