Supervisor: Dr. Marie-Isabelle Garcia
The gastrointestinal epithelium is one of the tissues with highest self-renewing rates under steady-state conditions, and it thereby constitutes an excellent model to better understand how tissues maintain homeostasis (1). In the past decade, intense research in this field has allowed identifying resident multipotent stem cells responsible for this task and has contributed to uncover the main molecular mechanisms associated with self-renewal and differentiation properties of these cells in the intestine under homeostasis. Upon injury, multiple types of active or quiescent stem cells showing potential interconversion have been reported. Regeneration can also be promoted through cell de-differentiation, a mechanism involving partial re-expression of a fetal transcriptomic program (2, 3, 4). The proposed PhD project aims to get further understanding on common and unique molecular and cellular mechanisms that are associated with epithelial fetal morphogenesis and adult regeneration. It will combine several complementary approaches, including in vivo studies using transgenic mice models as well as the 3D ex vivo culture technology, which offers the possibility to study mini-organs in a petri dish (5). This program will involve an interdisciplinary knowledge across molecular and cellular biology, transcriptomics, animal handling, tissue processing and immunohistological methods.
References
1. Stem Cells in Adult Homeostasis, Regeneration and Tissue Development of the Digestive Tract Epithelium (Review). Fernandez-Vallone V and Garcia MI. Int J Stem Cell Res Ther 2016, 3:038.
2. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage. Fernandez-Vallone V. et al. Development. 2016 143:14252-1463.
3. Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium. Mustata et al. Cell Reports. 2013 5:421-432.
4. Cold Atmospheric Plasma Differentially Affects Cell Renewal and Differentiation of Stem Cells and Apc-Deficient-Derived Tumor Cells in Intestinal Organoids. Cell Death Discovery. Hadefi et al. In press (2022).
5. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Sato et al. Nature 2009. 459:262–265.