| First Author | Giannini S | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 356 |
| PubMed ID | 31953383 | Mgi Jnum | J:284931 |
| Mgi Id | MGI:6387664 | Doi | 10.1038/s41467-019-14178-y |
| Citation | Giannini S, et al. (2020) beta4GALT1 controls beta1 integrin function to govern thrombopoiesis and hematopoietic stem cell homeostasis. Nat Commun 11(1):356 |
| abstractText | Glycosylation is critical to megakaryocyte (MK) and thrombopoiesis in the context of gene mutations that affect sialylation and galactosylation. Here, we identify the conserved B4galt1 gene as a critical regulator of thrombopoiesis in MKs. beta4GalT1 deficiency increases the number of fully differentiated MKs. However, the resulting lack of glycosylation enhances beta1 integrin signaling leading to dysplastic MKs with severely impaired demarcation system formation and thrombopoiesis. Platelets lacking beta4GalT1 adhere avidly to beta1 integrin ligands laminin, fibronectin, and collagen, while other platelet functions are normal. Impaired thrombopoiesis leads to increased plasma thrombopoietin (TPO) levels and perturbed hematopoietic stem cells (HSCs). Remarkably, beta1 integrin deletion, specifically in MKs, restores thrombopoiesis. TPO and CXCL12 regulate beta4GalT1 in the MK lineage. Thus, our findings establish a non-redundant role for beta4GalT1 in the regulation of beta1 integrin function and signaling during thrombopoiesis. Defective thrombopoiesis and lack of beta4GalT1 further affect HSC homeostasis. |
