Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance

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Science  06 Apr 2018:
Vol. 360, Issue 6384, pp. 106-110
DOI: 10.1126/science.aap8861

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Signaling hematopoietic stem cells from afar

Throughout our entire life span, hematopoietic stem cells (HSCs) generate all of our blood cells. The bone marrow microenvironment, or niche, is key to activating stem cell activity. Decker et al. now show that thrombopoietin generated in the liver, but not from the local bone marrow niche, maintains HSCs in vivo in mice. Thus, systemic endocrine factors are needed to maintain somatic stem cells from a distance. These findings may be important when considering how to stimulate HSCs for therapeutic use.

Science, this issue p. 106


Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using TpoDsRed-CreER knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of Tpo from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when Tpo is deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.

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