Hematopoietic Hierarchy - An Updated Roadmap.

The classical roadmap of hematopoietic hierarchy has been proposed for nearly 20 years and has become a dogma of stem cell research for most types of adult stem cells, including hematopoietic stem cells (HSCs). However, with the development of new technologies such as omics approaches at single-cell resolution, recent studies in vitro and in vivo have suggested that heterogeneity is a common feature of HSCs and their progenies. While these findings broaden our understanding of hematopoiesis, they also challenge the well-accepted hematopoietic hierarchy roadmap. Here, we review recent advances in the hematopoiesis field and provide an updated view to incorporate these new findings as well as to reflect on the complexity of HSCs and their derivatives in development and adulthood.

Zhang Y ，Gao S ，Xia J ，Liu F ... -  《-》

New paradigms on hematopoietic stem cell differentiation.

Cheng H ，Zheng Z ，Cheng T 《-》

Are transplantable stem cells required for adult hematopoiesis?

Hematopoietic stem cells (HSCs) have been studied intensely for more than half a century. As a result, the properties of HSCs have become a paradigm of adult stem cell biology and function. The "classical" view of hematopoiesis suggests that the HSCs sit at the top of a hierarchy and that differentiation involves sequential production of multipotent and lineage committed progenitors with limited self-renewal capacity. This view of hematopoiesis is certainly valid after transplantation of HSCs, where, with appropriate support, a single HSC can regenerate the entire hematopoietic system of the recipient. However, it is not clear whether HSCs perform the same function during steady-state hematopoiesis. Indeed, studies have shown that the majority of classical HSCs are not required for ongoing steady-state adult hematopoiesis. Several reports suggest that steady-state hematopoiesis relies on highly proliferative cells with more lineage restricted characteristics, a finding that was not anticipated based on results from transplantation experiments. However, other studies indicate a more substantial HSC contribution. Nevertheless, the notion of HSCs as distinct from progenitors appears to be simplistic in view of ample evidence for heterogeneity within the stem cell compartment. In this review we discuss recent results and controversies surrounding HSCs.

McRae HM ，Voss AK ，Thomas T 《-》

Revisiting the lineage contribution of hematopoietic stem and progenitor cells.

For a long time, self-renewing and multipotent hematopoietic stem cells (HSCs) have been thought to make a major contribution to both embryonic and adult hematopoiesis. The canonical hematopoietic hierarchy illustrating HSC self-renewal and multipotency has been established mainly based on invasive functional assays (e.g. transplantation or colony-forming units in the spleen and in culture), which evaluate the cellular potentials of HSCs. With the extensive applications of non-invasive cell fate-mapping strategies, recent lineage tracing-based studies have suggested that not all native hematopoiesis is established via the hierarchical differentiation of HSCs. By contrast, hematopoietic progenitor cells (HPCs) are a dominant contributor to both embryonic and young adult hematopoiesis. These new findings help redefine the cellular origins of embryonic and adult hematopoiesis under native conditions, and emphasize the differences in revealing HSC potential versus HSC fate using distinct approaches during stress and native hematopoiesis. Here, we review recent advances in HPC and HSC development, and provide an updated perspective to incorporate these new findings with our traditional understanding of developmental and adult hematopoiesis.

Gao S ，Zhang Y ，Liu F 《-》

Causes and Consequences of Hematopoietic Stem Cell Heterogeneity.

Blood and immune cells derive from multipotent hematopoietic stem cells (HSCs). Classically, stem and progenitor populations have been considered discrete homogeneous populations. However, recent technological advances have revealed significant HSC heterogeneity, with evidence for early HSC lineage segregation and the presence of lineage-biased HSCs and lineage-restricted progenitors within the HSC compartment. These and other findings challenge many aspects of the classical view of HSC biology. We review the most recent findings regarding the causes and consequences of HSC heterogeneity, discuss their far-reaching implications, and suggest that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field.

Haas S ，Trumpp A ，Milsom MD 《-》