Characterization of mammary cells derived from single cells with stem cell properties and organoid formation capacity by cell lineage tracing and cell tracking

Tissues and organs are generated during development and repaired over the lifetime by stem cells with extensive self-renewal and differentiation potential. The characteristics and the identity of the stem and differentiated cells are determined by specific transcription factors that act together with chromatin regulators to stabilize expression patterns that maintain the cell identities. Disruption of the chromatin state or changes in the expression levels of chromatin regulators is associated with cellular reprogramming, disease and oncogenesis. While a large number of chromatin regulators have been identified, the epigenomic processes by which stem cells differentiate remains largely unknown for some somatic stem cell types. Three dimensional organoid cultures generated from patient derived single cells with stem cells properties, allow for investigating regulators of the chromatin state and gene expression patterns in mammary gland normal or tumor development. In this work by using cell lineage tracing and cell tracking, I characterized homogenous populations of cells derived from single mammary cells with organoid formation capacity. My findings suggest that chromatin changes in the histone state of mammary cells both initiate and stabilize gene expression patterns before the establishment of lineage specifying transcription factors.