Yann Barrandon | EPFL Graph Search

Yann Barrandon graduated in Medicine in Paris where he also trained as a dermatologist and completed his PhD on the long term cultivation of human haematopoietic stem cells in 1982 under the direction of Dr. Catherine Dresch (Centre Hayem, St Louis Hospital). He worked as a post-doctoral fellow (1982-1983) with Pr. Marvin Karasek in the Department of Dermatology at Stanford University CA, and then with Pr. Howard Green, a pioneer in cell therapy, in the Department of Molecular and Cellular Physiology at Harvard Medical School (1983-1990). During this period, he participated in the world's first transplantations of epidermal stem cells on extensive third degree wounds and contributed several seminal findings including the demonstration of stem cells in cultures of human keratinocytes (PNAS 1987), and that human keratinocyte stem cells could be efficiently transduced by retroviral vectors (Science 1987), in collaboration with Richard Mulligan at the Whitehead Institute for Biomedical Research (Massachussets Institute of Technology, Cambridge, USA). He has also participated to the transfer of the stem cell technology from Harvard University to a spin off biotechnology company, now part of Genzyme Corp.

He returned to France in 1990 as Director of Research at the INSERM and Head of Lab at the Ecole Normale Supérieure, Paris. During this period, he demonstrated the presence of multipotent clonogenic stem cells in hair follicles (Cell 1994, 2001) and successfully brought stem cells from bench to bedside demonstrating the usefulness of a fibrin matrix to transplant epidermal stem cells. (Transplantation, 2000). Following his move to Lausanne, Yann Barrandon has shown that oligopotent stem cells are present in the mammalian cornea (Nature 2008), challenging previous dogma. He has also contributed to the characterisation of several skin diseases (Nature Genetics, 1993a, 1993b, 2000, 2005) and towards gene therapy of dystrophic epidermolysis bullosa. He is a partner in several EEC stem cell consortia (FP6: Therapeuskin and EuroStemCell, FP7: EuroSyStem, OptiStem, BetaCellTherapy).

Current research targets the role of small microenvironmental variations on stem cell behavior, and exploring the potency of stem cells of stratified epithelia (skin, esophagus, ocular surface) and of thymic epithelial cells. The lab is also involved in understanding the factors that regulate stem cell engraftment to improve epithelial cell therapy. An important aspect of the research aims at setting up a pilot clinical trial to demonstrate the feasibility of ex vivo gene therapy to treat Dystrophic Epidermolysis Bullosa, a rare but horrendous congenital disease of the skin that results in continuous blistering of the skin, chronic wounds, fusion of fingers and development of carcinoma.

Yann Barrandon was a member of the Faculty Council of the EPFL School of Life Sciences 2006-2008, of the Board of Swiss Stem Cell Network, 2004-2009, and is a member of the EPFL Ethics Committee since 2008. He is a reviewer for major scientific journals and for major granting agencies abroad. He is a member of the board of Directors of the International Society for Differentiation (ISD) and of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) and was a Member of the Board of Directors of the European Tissue Repair Society, 1990-1995. He was elected as EMBO member in 2009.

He has given over 300 invited conferences and seminars worldwide on the biology and the therapeutic use of cutaneous stem cells including:

Gordon Research Conferences, Tissue Repair and Regeneration, June 2005, New London, USA,

Keystone Symposia on Stem Cells, April 2006, Whistler, Canada

Keystone Symposia, Stem Cell Interactions with their Microenvironmental Niche, March 2007, Keystone, USA

Keystone Symposia, Stem Cell Niche Interactions, April 2009, Whistler, Canada

Gordon Research Conferences, Epithelial Stem Cells, June 2009, Les Diablerets, Switzerland

7th Meeting of the International Society Stem Cell Research, July 2009, Barcelona, Spain

16th International Society for Developmental Biologists, Edinburgh, Scotland, UK, Sept 2009

Yann Barrandon has given multiple media interviews and participated to different reportages:

LCI, TF1, France 2, France 3, RSR (Radio Suisse Romande), TSR (Television Suisse Romande), and articles in newspapers: Figaro, La Croix, Le Temps, LHebdo, Le Nouvelliste, etc. He was also a participant in the movie A Stem Cell Story, EuroStemCell, Best TV/video production, Tromsø Science Media Festival; Best short film, Scinema (Australia); In competition, Science Film Festival (Bangkok), BaKaFORUM 2007, Vedere la Scienza

He organized the second EuroStemCell international conference Advances in Stem Cell Research supported by the EMBO and held in Lausanne 8-10 September 2006. He regularly participates as faculty to the EEC funded Stem Cell Summer School held in Hydra Greece since 2005.

Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures

Fahd Azzabi Zouraq, Yann Barrandon, Thomas Michael Braschler, Jean-Baptiste Bureau, Kai Johnsson, Mako Kamiya, Johannes Alexander Mosig, Ariane Rochat

Adult autologous human epidermal stem cells can be extensively expanded ex vivo for cell and gene therapy. Identifying the mechanisms involved in stem cell maintenance and defining culture conditions to maintain stemness is critical, because an inadequate environment can result in the rapid conversion of stem cells into progenitors/transient amplifying cells (clonal conversion), with deleterious consequences on the quality of the transplants and their ability to engraft. Here, we demonstrate that cultured human epidermal stem cells respond to a small drop in temperature through thermoTRP channels via mTOR signaling. Exposure of cells to rapamycin or a small drop in temperature induces the nuclear translocation of mTOR with an impact on gene expression. We also demonstrate by single-cell analysis that long-term inhibition of mTORC1 reduces clonal conversion and favors the maintenance of stemness. Taken together, our results demonstrate that human keratinocyte stem cells can adapt to environmental changes (e.g., small variations in temperature) through mTOR signaling and constant inhibition of mTORC1 favors stem cell maintenance, a finding of high importance for regenerative medicine applications.

WILEY2023

Impedance-Based Single-Cell Pipetting

Yann Barrandon, Nicolas Jean Bernard Beuchat, David Vincent Bonzon, Jean-Baptiste Bureau, Georges Muller, Philippe Renaud, Nicolas Uffer

Many biological methods are based on single-cell isolation. In single-cell line development, the gold standard involves the dilution of cells by means of a pipet. This process is time-consuming as it is repeated over several weeks to ensure clonality. Here, we report the modeling, designing, and testing of a disposable pipet tip integrating a cell sensor based on the Coulter principle. We investigate, test, and discuss the effects of design parameters on the sensor performances with an analytical model. We also describe a system that enables the dispensing of single cells using an instrumented pipet coupled with the sensing tip. Most importantly, this system allows the recording of an impedance trace to be used as proof of single-cell isolation. We assess the performances of the system with beads and cells. Finally, we show that the electrical detection has no effect on cell viability.

SAGE PUBLICATIONS INC2020

Tp63-expressing adult epithelial stem cells cross lineages boundaries revealing latent hairy skin competence

Yann Barrandon, Paola Bonfanti, Stéphanie Claudinot, Christèle Gonneau, Daniel-Alexandre Littman, Ariane Rochat

The formation of hair follicles, a landmark of mammals, requires complex mesenchymal-epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus). Adult stem cells are thought to be fate restricted to lineages distinct to their tissue of origin. Here, the authors demonstrate that Tp63 expressing epithelial stem cells from several disparate tissues can respond to skin morphogenetic signals and contribute to hair follicles, sebaceous glands and/or epidermis.

NATURE RESEARCH2020