Platelet-specific SLFN14 deletion causes macrothrombocytopenia and platelet dysfunction through dysregulated megakaryocyte and platelet gene expression.

ABSTRACT: Schlafen 14-related (SLFN14-related) thrombocytopenia is a rare bleeding disorder caused by SLFN14 mutations altering hemostasis in patients with platelet dysfunction. SLFN proteins are highly conserved in mammals where SLFN14 is specifically expressed in megakaryocyte (MK) and erythroblast lineages. The role of SLFN14 in megakaryopoiesis and platelet function has not been elucidated. Therefore, we generated a murine model with a platelet- and MK-specific SLFN14 deletion using platelet factor 4 (PF4) Cre-mediated deletion of exons 2 and 3 in Slfn14 (Slfn14 PF4-Cre) to decipher the molecular mechanisms driving the bleeding phenotype. Slfn14 PF4-Cre+ platelets displayed reduced platelet signaling to thrombin, reduced thrombin formation, increased bleeding tendency, and delayed thrombus forma

SUBMITTER: Stapley RJ 

PROVIDER: S-EPMC12520693 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature