Identification of the role of SEL1L in platelet function through a multi-species genetic investigation.

Unlabelled: SEL1L is a well-known protein in the endoplasmic reticulum associated degradation (ERAD) pathway. While it is known to be expressed in platelets, SEL1L has never been shown to play an active role. Here we find evidence that SEL1L regulates platelet function.

Increased RhoA pathway activation downstream of αIIbβ3/SRC contributes to heterozygous Bernard Soulier syndrome.

Bernard Soulier syndrome (BSS) is a severe bleeding disorder with moderate to severe thrombocytopenia, giant platelets, and platelet dysfunction, caused by biallelic mutations in GP1BA, GP1BB, or GP9 genes. We generated induced pluripotent stem cells (iPSC) from a BSS patient with a novel heterozygous GP1BA p.N103D mutation, resulting in moderate macrothrombocytopenia.

In vitro studies of human erythropoiesis using a 3D silk-based bone marrow model that generates erythroblastic islands.

The pursuit of ex vivo erythrocyte generation has led to the development of various culture systems that simulate the bone marrow microenvironment. However, these models often fail to fully replicate the hematopoietic niche's complex dynamics. In our research, we use a comprehensive strategy that emphasizes physiological red blood cell (RBC) differentiation using a minimal cytokine regimen.