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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.

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

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 honors, awards and prizes

Swedish Research Council 

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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

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