PECAM-1: a multifaceted regulator of megakaryocytopoiesis.
PECAM-1 (CD31) knockout (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 hierarchic manner, functioning as a thermostat to "fine-tune" megakaryocytopoiesis.
Wu
Yue
Y
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT, USA.
Welte
Thomas
T
Michaud
Michael
M
Madri
Joseph A
JA
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D006411:Hematopoiesis, Extramedullary / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010976:Platelet Count; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D034061:Thrombopoiesis / Q000502:physiology*
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019009:Proto-Oncogene Proteins c-kit