Genodermatoses
Team :
Christine Baldeschi : Professor (UEVE)
Xavier Nissan : Associate engineer (CECS)
Jessica Feteira : PhD Student
Manoubia Saidani : Qualified research technician (CECS)
Lionel Larribère : Associate scientist (CECS)
Our group is focused on the development of protocols of differentiation of human embryonic stem cells into epidermal cells.
The hidrotic ectodermal dysplasia or Clouston syndrome is a very complex and rare dominant genodermatose characterized by abnormal development of the skin and appendages (hair, nails, teeth and sweat glands). In fact, patients develop a palmoplantar hyperkeratosis, a generalized alopecia and a dysplasy of the nails. The disease is caused by mutations in the human GJB6 gene which encodes the gap junction protein connexin 30.
For the rare skin disease it’s very difficult to obtain skin biopsies of these patients to have ex vivo keratinocyte amplification allowing a characterization and a treatment of these genodermatoses.
In these situations, the potential of human embryonic stem cells (hES) to be differentiated into ectodermal precursors give the hope to understand the developmental steps leading to the generation of epidermal stem cells. Moreover, the characterization of the key signalling pathways involved in skin morphogenesis will be translated into therapeutic benefit for the skin disease.
The implementation and improvement of these novel treatment strategies require the development of a protocol of differentiation from the hES into keratinocyte.
These keratinocytes derived from the hES must be similar to those naturally present in the basal layer of the skin, where they allow the constant renewal of the skin via the mechanism represented below.
The hidrotic ectodermal dysplasia or Clouston syndrome is a very complex and rare dominant genodermatose characterized by abnormal development of the skin and appendages (hair, nails, teeth and sweat glands). In fact, patients develop a palmoplantar hyperkeratosis, a generalized alopecia and a dysplasy of the nails. The disease is caused by mutations in the human GJB6 gene which encodes the gap junction protein connexin 30.
For the rare skin disease it’s very difficult to obtain skin biopsies of these patients to have ex vivo keratinocyte amplification allowing a characterization and a treatment of these genodermatoses.
In these situations, the potential of human embryonic stem cells (hES) to be differentiated into ectodermal precursors give the hope to understand the developmental steps leading to the generation of epidermal stem cells. Moreover, the characterization of the key signalling pathways involved in skin morphogenesis will be translated into therapeutic benefit for the skin disease.
The implementation and improvement of these novel treatment strategies require the development of a protocol of differentiation from the hES into keratinocyte.
These keratinocytes derived from the hES must be similar to those naturally present in the basal layer of the skin, where they allow the constant renewal of the skin via the mechanism represented below.
Development of differentiation protocols to obtain hES-derived keratinocytes :
The first part of the project consisted in the development of protocols allowing the obtention of hES-derived keratinocytes.
Preliminary experiments using a specific medium of differentiation on feeder culture layer allow the hES to be differentiated in epithelial cells.
Preliminary experiments using a specific medium of differentiation on feeder culture layer allow the hES to be differentiated in epithelial cells.
Epidermis reconstitution :
In order to check the ability of this population of hES-derived keratinocytes to generated cohesive and stratified epithelia with all the characteristics of normal epidermis, including a long term self-renewal, we plan to graft these skin equivalents in nude mice.
