Prolonged Maintenance of Hematopoietic Stem Cells That Escape from Thrombopoietin Deprivation

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2021 Mar 3

PMID 33657206

Citations 1

Authors

Ayako Nakamura-Ishizu

Desmond Wai Loon Chin

Takayoshi Matsumura

Darren Qiancheng Tan

Makiko Mochizuki-Kashio

Deng Jianwen

Toshio Suda

Affiliations

Soon will be listed here.

Abstract

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.

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