Researchers Unravel Novel Insights on Hematopoietic Stem Cell (HSC) Maintenance and its Mechanism Under Thrombopoietin (Thpo) Deficiency

Hematopoietic stem cells (HSC) residing in the bone marrow are essential for life-long hematopoiesis. To ensure long term regenerative potential in HSCs, the preservation of HSCs in its quiescent state is crucial and constitutes a fundamental property of HSCs. While the regulation of HSCs has been extensively studied, the key regulatory mechanism of how quiescence is acquired remains unaddressed. In this study, a team of researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS), the International Research Center for Medical Sciences (IRCMS) at the Kumamoto University and the Tokyo Women’s Medical University (TWMU) investigated the maintenance of HSCs in quiescence as well as its association with cytokine Thrombopoietin (Thpo).

While earlier studies established that Thpo induces quiescence and promotes self-renewal divisions in HSCs, the effect of Thpo on HSC remains perplexing. To clarify the contradictory effect of Thpo, the research team, which includes Prof. Toshio Suda and Dr. Ayako Ishizu, utilized the gene knockout mouse model and found that the administration of a Thpo receptor agonist, Romiplostim, to Thpo-deficient mice can stimulate the expansion of quiescent HSC numbers.

By performing Thpo signalling, the team also identified changes in cell metabolism in mitochondria, autophagy and protein synthesis. Collectively, their data implies that Thpo signalling elicits wide-ranging response in HSCs.

With this newly established understanding of how Thpo signaling maintains HSC function, findings from this study reveals the therapeutic merits and rationale of Thpo receptor agonists, holding promise for improved therapeutic treatment options for other HSC-related diseases.

Moving forward, the team intends to further evaluate the function of Thpo in regulating lifelong hematopoiesis, as well as the effect of Thpo/cytokine signalling, which will help address questions on what regulated organelle turnover and how organelles network in HSC.

Read the full study here.