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Publication : Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance.

First Author  Decker M Year  2018
Journal  Science Volume  360
Issue  6384 Pages  106-110
PubMed ID  29622652 Mgi Jnum  J:272167
Mgi Id  MGI:6282621 Doi  10.1126/science.aap8861
Citation  Decker M, et al. (2018) Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance. Science 360(6384):106-110
abstractText  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 Tpo(DsRed-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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