Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis.

Characterization of hematopoietic stem cells (HSCs) has advanced largely owing to transplantation assays, in which the developmental potential of HSCs is assessed generally in nonhomeostatic conditions. These studies established that adult HSCs extensively contribute to multilineage hematopoietic regeneration upon transplantation. On the contrary, recent studies performing lineage tracing of HSCs under homeostatic conditions have shown that adult HSCs may contribute far less to steady-state hematopoiesis than would be anticipated based on transplantation assays. Here, we used 2 independent HSC-lineage-tracing models to examine the contribution of adult HSCs to steady-state hematopoiesis. We show that adult HSCs contribute robustly to steady-state hematopoiesis, exhibiting faster efflux toward the myeloid lineages compared with lymphoid lineages. Platelets were robustly labeled by HSCs, reaching the same level of labeling as HSCs by 1 year of chase. Our results support the view that adult HSCs contribute to the continuous influx of blood cells during steady-state hematopoiesis.

Chapple RH ，Tseng YJ ，Hu T ，Kitano A ，Takeichi M ，Hoegenauer KA ，Nakada D ... -  《-》

In-vivo differentiation of adult hematopoietic stem cells from a single-cell point of view.

Nazaraliyev A ，Richard E ，Sawai CM 《-》

Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging.

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.

Säwen P ，Eldeeb M ，Erlandsson E ，Kristiansen TA ，Laterza C ，Kokaia Z ，Karlsson G ，Yuan J ，Soneji S ，Mandal PK ，Rossi DJ ，Bryder D ... -  《-》

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 《-》

CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age.

Gekas C ，Graf T 《-》