Stem cells, development and cancer
Our group is studying
- The cellular and molecular mechanisms regulating cell fate specification during embryonic development and tissue homeostasis.
During embryonic development, undifferentiated progenitors cells are progressively specified to adopt a particular cell fate. To dissect the molecular mechanisms involved in cell fate specification, we are studying the differentiation of embryonic stem cells in-vitro. Embryonic stem cells present the great advantage to be easily genetically modified and their in-vitro differentiation recapitulates relatively well normal embryonic development. We are studying cardiac specification as a model because the heart is the first organ to develop during embryogenesis, cardiac differentiation is induced by a robust and well-characterized key regulator genes conserved from Drosophila to human, and present important clinical implications.
- The role of adult stem cells during cancer initiation.
Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. However, for most cancer it is still unknown whether the initial oncogenic mutations arise in adult stem cells or in more committed cells that re-acquire stem cell-like properties. We are determining whether epithelial SCs are the initial target cells of oncogenic mutations during cancer formation and represent the natural niche for pre-cancerous cells. Using mice genetics, we are also exploring the influence of the pre-existing self-renewing capacity of adult SC during cancer formation.
- The role of cancer stem cells during cancer growth and relapse after therapy.
Recent studies provide compelling evidence that certain leukemia and human solid tumors contain cells with high clonogenic potential, capable of reforming parental tumor upon transplantation, and which have been referred to as cancer stem cells (CSC). However, it remains unclear whether all cancers contain CSCs and how do CSCs contribute to the actual tumor growth. We are using in this project different approaches combining cell isolation and transplantation as well as unbiased genetic approach to determine the contribution of CSC during cancer growth and relapse after therapy of different epithelial cancers.
Main recent publications
Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E.
Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
Cell. 2004 118(5):635-48. Featured article accompanied by a preview.
Blanpain C, Lowry WE, Pasolli A, and Fuchs E.
Canonical notch signaling functions as a commitment switch in the epidermal lineage.
Genes Dev. 2006, 20:3022-35. Cover article.
Lowry, WE.*, Blanpain C.*, Nowak JA., Guasch G., Lewis L. and Fuchs E. *
denotes co-first author. Defining the impact of b-catenin/Tcf transactivation on epithelial stem cells.
Genes Dev. 2005 (13):1596-611. Cover article.
Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E.
Defining the epithelial stem cell niche in skin.
Science. 2004 303:359-63.
Blanpain C, Horsley V, Fuchs E.
Epithelial Stem Cells: Turning over New Leaves.
Cell. 2007, 128:445-58.
Blanpain C, Fuchs E.
Epidermal stem cells of the skin.
Annu Rev Cell Dev Biol. 2006; 22:339-73.
Blanpain C, Fuchs E.
p63: revving up epithelial stem-cell potential.
Nat Cell Biol. 2007 (7):731-3.