Catherine Robin, group leader at the Hubrecht Institute, was recently invited by FEBS Letters to be the main guest editor of a special issue on hematopoietic stem cells (HSCs). In this special issue, international experts discuss the current understanding of hematopoietic stem cell (HSC) generation as well as recent exciting fundamental and technical developments and also share their views on future research directions. Altogether, the reviews highlight the importance to understand the fundamentals of the hematopoietic production and homeostasis under physiological condition to understand the deregulation occurring in pathological situation. Such knowledge will be increasingly exploited in the future for therapeutic purposes, drug testing and discovery.

Hematopoietic stem cells (HSCs) have been the focus of intense research since scientists introduced the “stem cell” theory at the beginning of the 20th century. Major discoveries, sometimes serendipitous, have paved the way to our present concept of HSCs and blood formation. The inherent multipotency and self-renewal properties confer to HSCs the capacity to reestablish the entire hematopoietic system and therefore to cure the thousands of patients affected with blood related diseases every year. HSC transplantations are widely performed in case of cancers of the hematopoietic system (e.g. leukemia, lymphoma), to replenish the cells lost after high-doses of chemotherapy on solid tumors, or to resist autoimmune diseases. However, the shortage of HSCs available for the clinic has led to an increasing number of patients in long-term waiting list for compatible HSC transplant. This important limitation has warranted investigation aiming to either amplify HSCs in vitro or to find an alternative cell supply to donor HSCs. A very attractive solution would be to de novo produce large quantities of tailor-made HSCs. However, recapitulating all steps leading to HSC production in vitro has proven to be very challenging. A better understanding of HSC fate determination, generation and regulation, as it occurs in vivo in the course of embryonic and adult life, represent a pre-requisite to determine what a cell needs to become and to remain a transplantable HSC in a Petri dish.

The Special Issue of FEBS Letters is a collection of review articles authored by invited international experts in various fields. The issue is divided in four main topics. The first topic covers hematopoietic stem and progenitor cell production during the embryonic development of different species (Drosophila, zebrafish, xenopus, mouse as well as human). The second topic covers the molecular control of hematopoietic specification and differentiation, embracing genetic programming, chromatin landscape regulation, epigenetic regulation and the dynamics of enhancer landscape. The third topic covers the recent progresses made toward developing new techniques (e.g. single cell RNA-sequencing, mass cytometry, integration site barcoding, cellular barcoding and transposon barcoding) and design computational models to better understand, and sometimes revisit, our concepts of cell heterogeneity, cell lineage differentiation and regulatory relationships. The fourth topic covers the recent progresses and future prospects for in vitro HSC production. The generation of tailor-made HSCs in vitro via directed differentiation of pluripotent stem cells (e.g. ES cells, iPS cells), or the reprogramming of somatic cells, represents the Holy Grail since decades. Although this field is in its infancy, tremendous progresses have been recently made.

FEBS Lett. 2016 Nov;590(22)