During embryonic development, hematopoietic cells originate from a series of hematopoietic waves that occur at different time points and produce cells with specific characteristics. The last hematopoietic wave is the one that gives rise to definitive hematopoietic stem cells (HSCs), which are single-handedly capable of self-renewal and multi-lineage differentiation. At the cellular level, HSCs arise from arterial hemogenic endothelium (HE) – a cell type that has not been fully characterized – through a process called endothelial to hematopoietic transition (EHT), mainly in the aorta-gonad-mesonephros (AGM) region. Next, HSCs migrate to the fetal liver and later to the bone marrow, where hematopoiesis occurs during adulthood. Although HSCs have been extensively studied in adult human and animal settings, further studies are needed to describe and characterize hematopoiesis during development elaborately.

Methods describing how to visualize the emergence of HSCs, facilitate the culture of HE in vitro, reproduce the conditions in which the EHT process occurs, and identify and characterize HSCs in the AGM, fetal liver, and bone marrow are essential to understanding HSC development better. This Methods Collection aims to provide state-of-the-art techniques and protocols for studying developmental hematopoiesis in vivo and in vitro.

In the long term, elucidating the mechanisms by which HSCs arise during development would allow the in vitro production of functional and transplantable cells: an essential stem cell therapy for treating genetic diseases and hematopoietic malignancies.