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Thrombopoietin maintains megakaryopoietic HSPC
nant romiplostim and the small molecule eltrombopag have been approved as clinical MPL agonists. We showed that treatment of Thpo-KO mice with romiplostim can res- cue platelet numbers, indicating that megakarypoietic potential is partially cell-intrinsic. Further investigation may reveal the mechanisms through which THPO/MPL signaling drives expansion of HSPC and its role in self- renewal division of megakaryopoietic HSPC.
This study addresses the many conflicting reports of the role of THPO in HSPC quiescence/self-renewal division as well as its role in megakaryocyte differentiation. It identi- fies specific HSPC populations that depend on THPO as well as showing that THPO may not be directly responsi- ble for the loss of quiescence observed in THPO KO mod- els, resolving previous contradictory findings.
Disclosures
No conflicts of interest to disclose.
Contributions
AO’N conceived and designed the study, collected, analyzed and interpreted data and wrote the manuscript. DC wrote the manuscript; DT and A’QBBAM collected data. AI-N provided study materials and collected data. TS conceived and designed the study, organized financial support and gave final approval of the manuscript.
Acknowledgments
The authors thank Dr. Md. Zakir Hossain at CSI, NUS for assistance in the design and generation of the Thpo flox mice and Prof. Qingde Wang of University of Pittsburgh Medical Center for kindly providing Alb-Cre mice.
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