Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver
Xiaolin Ma,
Yun Li,
Yuji Kondo,
Huiping Shi,
Jingjing Han,
Yizhi Jiang,
Xia Bai,
Stephanie A. Archer-Hartmann,
Parastoo Azadi,
Changgeng Ruan,
Jianxin Fu,
Lijun Xia
Affiliations
Xiaolin Ma
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou; Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao
Yun Li
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou
Yuji Kondo
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
Huiping Shi
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
Jingjing Han
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou
Yizhi Jiang
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou
Xia Bai
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou
Stephanie A. Archer-Hartmann
Complex Carbohydrate Research Center, University of Georgia, Athens, GA
Parastoo Azadi
Complex Carbohydrate Research Center, University of Georgia, Athens, GA
Changgeng Ruan
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou
Jianxin Fu
Oklahoma Medical Research Foundation
Lijun Xia
Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
Sialic acid is a common terminal residue of glycans on proteins and acidic sphingolipids such as gangliosides with important biological functions. The sialylation process is controlled by more than 20 different sialyltransferases, many of which exhibit overlapping functions. Thus, it is difficult to determine the overall biological function of sialylation by targeted deletion of individual sialyltransferase. To address this question, we established a mouse line with the Slc35a1 gene flanked by loxP sites. Slc35a1 encodes the CMP-sialic acid transporter that transports CMP-sialic acid from cytoplasm into the Golgi apparatus for sialylation. Here we report our study regarding the role of sialylation on megakaryocytes and platelets using a mouse line with significantly reduced sialylation in megakaryocytes and platelets (Plt Slc35a1-/-). The major phenotype of Plt Slc35a1-/- mice was thrombocytopenia. The number of bone marrow megakaryocytes in Plt Slc35a1-/- mice was reduced, and megakaryocyte maturation was also impaired. In addition, an increased number of desialylated platelets was cleared by Kupffer cells in the liver of Plt Slc35a1-/- mice. This study provides new insights into the role of sialylation in platelet homeostasis and the mechanisms of thrombocytopenia in diseases associated with platelet desialylation, such as immune thrombocytopenic purpura and a rare congenital disorder of glycosylation (CDG), SLC35A1-CDG, which is caused by SLC35A1 mutations.
