Uterine Epithelial Fate Specification

The genetic and molecular mechanisms of epithelial cell differentiation and regeneration are understudied and poorly understood. Different cell types have been identified as putative endometrial epithelial stem cells, including bone marrow-derived cells, hematopoietic stem cells, pericytes, and a subset of uterine epithelial and stromal cells. However, the findings remain ambiguous and inconclusive. Given the complexity of the epithelial lineages of the endometrium and their cyclic regeneration, it is difficult to conceive that a single epithelial stem cell population is capable of such a high level of regenerative turnover. Therefore, this proposal focuses more on the process used by the uterus to replace lost cells, rather than on the physical entity of a stem cell. The alternative hypothesis to the classical stem cell model is that the endometrium contains facultative stem cells (FSC) that can function as transient stem cells during tissue regeneration and repair in adults as well as during developmental processes. The goal of this area of research in the Lab is to incorporate innovative organoid and cell culture methods, in combination with in vivo mouse models, and advanced single cell genomic and transcriptomic technologies to decipher the mechanisms governing epithelial fate specification.

Specifically, these studies aim to address:

1. Cell type heterogeneity and cell-specific differences in development and regeneration.

2. Discern critical biological pathways driving endometrial epithelial development

3. Identify potential biomarkers of perturbations in development and disease.