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, totipotency and pluripotency is established in the early human embryo.

2. Develop embryonic stem cell based strategies. We have establish a first clinically compliant good manufacturing practice (GMP) grade human embryonic stem cell line, KARO1.

3. Treatment of Diabetes. We are actively working to establish methodology both to efficiently produce glucose responsive beta cells and evaluate the optimal way to deliver these to the patient. We are particularly interested in exploring the anterior chamber of the eye as an alternative site of transplantation.

4. Treatment of age-related macula degeneration (AMD). During collaborative agreement with St. Erik Eye Hospital and Novo Nordisk A/S we have manufactured hESC-RPE cells (CellThRPE1) according to our developed protocol and performed preclinical toxicology and functionality testing. With the support of Erling-Persson Foundation, we are now aiming to initiate clinical trial for treatment of AMD. Additional partners are welcomed to contact us. We continue to advance related methodologies and increase our fundamental knowledge of how the different cell types of the retina are established during embryogenesis and in vitro.

 

Current Lab members

Dr. Elisabeth Moussaud, Research Coordinator Lanner and Damdimopoulou lab

Dr. Cheng Zhao, Research Specialist shared with Sophie Petropoulos. Bioinformatics in embryo and stem cell biology.

Dr. Sanjiv Risal, Research specialist within Acharya lab. Spatial transcriptomics of embryo development.

Dr. Shivam Chandel, Postdoc. Developing insulin producing stem cell derived islets.

Dr. Mathilde Bergamelli, Postdoc shared with Andres Salumets. Using blastoids to mimic embryo implantation biology.

Dr. Jing Lyu, Postdoc performing epigenetic studies or early human embryos.

Laura Baque Vidal, PhD student. Genetic engineering to combat transplantation rejection and establishing validated release criteria for CellThRPE1.

Sara Saietz, PhD student. Embryonic stem cell-based treatment of retinal degenerative disease

Frederik Bär, PhD student. Individualized iPSC-based treatment of blindness

 

Past Lab members

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

Dr. Sebastian Hildebrand, Postdoc. Now working at Tecan

Dr. Liselotte Antonsson, Now working at Stockholm University

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

Dr. Siqin Wu, Industrial Postdoc at Spiber Technologies.

Dr. Sandra Petrus-Reurer, PhD and Postdoc, now working at Cambridge University. 

Dr. Sara Padrell Sánchez, PhD student now Director of Business Development at Healios

Dr. John Paul Schell. PhD and Postdoc now working in Professor Ken Chiens laboratory, KI

Dr. Paschalis Efstathopoulos, Industrial Postdoc now working as Research scientist at Novo Nordisk

Dr. Leni Wagner, PhD and Postdoc.

Dr. Alvaro Plaza Reyes, PhD and Postdoc. Currently working at CABIMER, Spain

Dr. Pankaj Kumar, Postdoc. Currently at Université libre de Bruxelles, Belgium

Dr. Nicholas Ortega, Postdoc. Currently working at Bio-Techne, Sweden

Dr. Heather Main, ATMP Sweden

Dr Jere Weltner, Postdoc. Currently at University of Helsinki

Dr. Breniere-Letuffe, Postdoc

Hazel Reilly, Currently PhD student at Karolinska Institutet, Sweden

Nerges Winblad, PhD student. 

Mona Hedenskog, Previous lab manager, currently enjoying retirement.

Nefeli Eirini Beri, Previous MSc student

Hugo Metzger, Previous Erasmus student

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.

 

Publications

 

Complete human day 14 post-implantation embryo models from naïve ES cells

B. Oldak, E. Wildschutz, V. Bondarenko, A. Aguilera-Castrejon, C. Zhao, S. Tarazi, M-Y. Comar, S. Ashouokhi, D. Lokshtanov, F. Roncato, S. Viukov, E. Ariel, M. Rose, N. Livnat, T. Shani, C. Joubran, R. Cohen, Y. Addadi, M. Kedmi, H Keren-Shaul, V Pasque, S Petropoulos, F. Lanner, N. Novershtern, J. Hanna. Nature 2023

Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome

C.H. Chan, Y.Y. Lam, N. Wong, L. Geng, J. Zhang, V. Ahola, A. Zare, R.A. Li, F. Lanner, W. Keung, Y-F. Cheung. Communications Biology 2023

The continued absence of functional germline stem cells in adult ovaries.

Yoshihara M, Wagner M, Damdimopoulos A, Zhao C, Petropoulos S, Katayama S, Kere J, Lanner F, Damdimopoulou P. Stem Cells 2022

Molecular profiling of retinal pigment epithelial cell differentiation for therapeutic use

Petrus-Reurer S, Lederer AR, Baqué-Vidal L, Douagi I, Pannagel B, Aronsson M, Bartuma H, Wagner M, André H, Sundström E, Bhaduri A, Kriegstein A, Kvanta A, La Manno G, Lanner F. Stem Cell Reports 2022

Polycomb Repressive Complex 2 shields naïve human pluripotent cells from trophectoderm differentiation

Kumar B, Navarro C, Winblad N, Schell JP, Zhao C, Weltner J, Baque-Vidal L, Salazar Mantero, Petropoulos S, Lanner F, Elsässer SJ. Nature Cell Biology 2022

A peek into the black box of human embryology

Goedel A, Lanner F Nature 2021

Refined transcriptional blueprint of human preimplantation embryos

Weltner J and Lanner F Cell Stem Cell 2021

Amnion signals are essential for mesoderm formation in primates

Yang R, Goedel A, Kang Y, Si C, Chu C, Zheng Y, Chen Z, Gruber PJ, Xiao Y, Zhou C, Witman N, Leung CY, Chen Y, Fu J, Ji W, Lanner F, Niu Y, Chien K. Nat Commun. 2021 Browse the transcriptional atlas here

All models are wrong, but some are useful: Establishing standards for stem cell-based embryo models

Posfai E, Lanner F, Mulas C, Leitch HG. Stem Cell Reports 2021

Reprogrammed iBlastoids contain amnion-like cells but not trophectoderm

Zhao C, Plaza Reyes A, Schell JP, Weltner J, Ortega N, Zheng Y, Björklund ÅK, Rossant J, Fu J, Petropoulos S, Lanner F. BioRxiv 2021

Evaluating totipotency using criteria of increasing stringency

Posfai E, Schell JP, Janiszewski A, Rovic I, Murray A, Bradshaw B, Yamakawa T, Pardon T, El Bakkali M, Talon I, De Geest N, Kumar P, To SK, Petropoulos S, Jurisicova A, Pasque V, Lanner F and Janet Rossant. Nature Cell Biology, 2021

Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells.

Plaza Reyes A, Petrus-Reurer S, Padrell Sánchez S, Kumar P, Douagi I, Bartuma H, Aronsson M, Westman S, Lardner E, André H, Falk A, Nandrot EF, Kvanta A, Lanner F. Nat Commun. 2020

Preclinical safety studies of human embryonic stem cell-derived retinal pigment epithelial cells for the treatment of age-related macular degeneration.

Petrus-Reurer S, Kumar P, Padrell Sánchez S, Aronsson M, André H, Bartuma H, Plaza Reyes A, Nandrot EF, Kvanta A, Lanner F. Stem Cells Transl Med. 2020

Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells Lacking Human Leukocyte Antigen Class I and II.

Petrus-Reurer S, Winblad N, Kumar P, Gorchs L, Chrobok M, Wagner AK, Bartuma H, Lardner E, Aronsson M, Plaza Reyes Á, André H, Alici E, Kaipe H, Kvanta A, Lanner F. Stem Cell Reports. 2020

Karolinska Institutet Human Embryonic Stem Cell Bank

Main H, Hedenskog M, Acharya G, Hovatta O, Lanner F. Stem Cell Research. 2020

Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells.

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

Nat Commun. 2020.    Browse the transcriptional data in our Eovary

Phosphoproteomics identifies a bimodal EPHA2 receptor switch that promotes embryonic stem cell differentiation.

Fernandez-Alonso R, Bustos F, Budzyk M, Kumar P, Helbig AO, Hukelmann J, Lamond AI, Lanner F, Zhou H, Petsalaki E, Findlay GM. Nat Commun. 2020

Human induced pluripotent stem cells from two azoospermic patients with Klinefelter syndrome show similar X chromosome inactivation behavior to female pluripotent stem cells.

Panula S, Kurek M, Kumar P, Albalushi H, Padrell Sánchez S, Damdimopoulou P, Olofsson JI, Hovatta O, Lanner F, Stukenborg JB. Hum Reprod. 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.

Academic honours, awards and prizes

Vinnova precision medicin centre IndiCell

Novo Nordisk collaborative support

Wallenberg Academy Fellow

Swedish Research Council 

Swedish Foundation for Strategic Research                    

Ragnar Söderberg Foundation

Mats Sundin Fellowship

ÅKE WIBERGS STIFTELSE

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

CIMED

Knut och Alice Wallenbergs Stiftelse