| First Author | Nakamura-Ishizu A | Year | 2021 |
| Journal | Blood | Volume | 137 |
| Issue | 19 | Pages | 2609-2620 |
| PubMed ID | 33657206 | Mgi Jnum | J:326345 |
| Mgi Id | MGI:6724792 | Doi | 10.1182/blood.2020005517 |
| Citation | Nakamura-Ishizu A, et al. (2021) Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation. Blood 137(19):2609-2620 |
| abstractText | Hematopoietic stem cells (HSC) rarely divide, rest in quiescence, and proliferate only upon stress hematopoiesis. The cytokine thrombopoietin (Thpo) has been perplexingly described to induce quiescence and promote self-renewal divisions in HSCs. To clarify the contradictory effect of Thpo, we conducted a detailed analysis on conventional (Thpo-/-) and liver-specific (Thpofl/fl;AlbCre+/-) Thpo-deletion models. Thpo-/- HSCs exhibited profound loss of quiescence, impaired cell cycle progression, and increased apoptosis. Thpo-/- HSCs also exhibited diminished mitochondrial mass and impaired mitochondrial bioenergetics. Abnormal HSC phenotypes in Thpo-/- mice were reversible after HSC transplantation into wild-type recipients. Moreover, Thpo-/- HSCs acquired quiescence with extended administration of a Thpo receptor agonist, romiplostim, and were prone to subsequent stem cell exhaustion during competitive bone marrow transplantation. Thpofl/fl;AlbCre+/- HSCs exhibited similar stem cell phenotypes but to a lesser degree compared with Thpo-/- HSCs. HSCs that survive Thpo deficiency acquire quiescence in a dose-dependent manner through the modification of their metabolic state. |
