Submitted May 22, 2006
Accepted April 3, 2007
PECAM-1: A multifaceted regulator of megakaryocytopoiesis
Yue Wu, Thomas Welte, Michael Michaud, and Joseph A. Madri*
Dept of Pathology, Yale University School of Medicine, New Haven, CT, United States
* Corresponding author; email: joseph.madri{at}yale.edu.
PECAM-1 (CD31) KO mice exhibit excessive megakaryocytopoiesis, accompanied by increased numbers of megakaryocytes associated with the stromal niche rather than the vascular niche. During earlier stages of megakaryocytopoiesis in KO marrow, an expanded Lin-Sca-1+c-kit+ hematopoietic stem cell (HSC) population and increased quiescent Lin- progenitor pool were identified. During the later stages of megakaryocytopoiesis, CD31KO megakaryocytes exhibited abnormal adhesion/transmigration behaviors. Lastly, KO animals exhibited excessive splenic extramedullary megakaryocytopoiesis, which likely compensates for the impaired marrow megakaryocytopoiesis, resulting in normal peripheral platelet number. Thus PECAM-1 modulates megakaryocytopoiesis in a hierarchical manner, functioning as a thermostat to "fine-tune" megakaryocytopoiesis.
