Haematopoietic progenitors restrict their fate sooner than previously considered

One of the main goals of the DECIDE project has been to investigate and understand the process by which blood cells are continuously generated throughout life.

Such knowledge can be of paramount importance for the treatment of haematopoietic malignancies. All blood cells are derived from haematopoietic stem cells and the precise developmental “road” that stem cells take to differentiate to mature blood cells is still unknown and currently under intense investigation and debate. One of the most important questions still unanswered in this research field is how early in development haematopoietic progenitors restrict their developmental options and therefore lose their multi-lineage potential. In the present study, research from Prof. A. Rolink’s laboratory made use of cutting-edge technology in order to analyze gene expression and developmental potential of a progenitor population (EPLM) previously identified by the group, at the single-cell level. Analysis of single cells showed that this population, which was previously considered to contain cells able to give rise to both myeloid and lymphoid lineages, is instead composed of a mix of cells with restricted developmental potentials, either to myeloid or to lymphoid fates. Thus, the results of the analysis indicate that haematopoietic progenitors become restricted to particular developmental cell fates earlier than considered before. In addition, the study is an example of how recent technological advances can lead to breakthrough discoveries, which might revise current concepts in haematopoiesis.

• Alberti‐Servera L, von Muenchow L, Tsapogas P, Capoferri G, Eschbach K, Beisel C, Ceredig R,  Ivanek R, Rolink A. Single-cell RNA sequencing reveals developmental heterogeneity among early lymphoid progenitors. EMBO Journal, 2017, doi :10.15252/embj.201797105