Lessons from early life: understanding development to expand stem cells and treat cancers.

Haematopoietic stem cell (HSC) self-renewal is a process that is essential for the development and homeostasis of the blood system. Self-renewal expansion divisions, which create two daughter HSCs from a single parent HSC, can be harnessed to create large numbers of HSCs for a wide range of cell and gene therapies, but the same process is also a driver of the abnormal expansion of HSCs in diseases such as cancer. Although HSCs are first produced during early embryonic development, the key stage and location where they undergo maximal expansion is in the foetal liver, making this tissue a rich source of data for deciphering the molecules driving HSC self-renewal.

Identification and characterization of in vitro expanded hematopoietic stem cells.

Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200-fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non-HSCs and single cell-initiated cultures have substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures.