Leading Edge Techniques in the Quest for Characterizing Rare Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) occupy the summit of the intricate hematopoiesis hierarchy, constituting a mere 0.01% of the adult bone marrow. The rarity of these cells poses a challenge in exploring their biological intricacies. Historically, research efforts grappled with this scarcity, often investigating broader cell populations that encompass multipotent progenitor cells, with HSCs representing only a modest 2–5%. Consequently, a crucial necessity emerged for methodologies accommodating the constraints imposed by the low abundance of HSCs.

In the last decade, the landscape has transformed with the advent of multi-omics technologies, such as single-cell-based approaches encompassing proteomics, metabolomics, transcriptomics, and epigenetics. These advancements, coupled with refined ex vivo and in vivo models of stem cells, have ushered in a new era where the independent study of HSCs has become feasible. Notably, strides in humanized models have further enriched the scientific toolkit, enabling the validation of HSC biology within human systems.

This review attempts to spotlight recent breakthroughs and their associated advantages and disadvantages, collectively illuminating the avenues that now exist for delving into the intricate biology of functional HSCs.