Role of SALL4 in hematopoiesis

Purpose of review Stem cell gene SALL4 has been well characterized for its essential role in developmental events as well as embryonic stem cell pluripotency maintenance. Several current reports now shed new light on its functions in regulating hematopoietic cell self-renewal and differentiation. In this review we attempt to summarize SALL4 roles for normal hematopoiesis, and how the knowledge obtained can be used to develop advanced cell therapies. Recent findings SALL4 may act as a critical controller to regulate the fate of hematopoietic cells. In normal bone marrow, SALL4 is selectively expressed in primitive hematopoietic precursors and rapidly downregulated following differentiation. Of particular interest, SALL4 isoforms are able to stimulate large scale ex-vivo expansion of hematopoietic stem/progenitor cells (HSCs/HPCs). The SALL4 expanded HSCs/HPCs retain multilineage repopulation and long-term engraftment activities, which are clinically meaningful. The stem cell self-renewal mediated by SALL4 is linked to epigenetic machinery. Summary The emerging knowledge about how SALL4 regulates HSC behavior may be used in the near future to develop advanced cell therapies, for example, through large-scale stem cell expansion ex vivo.