E-cadherin expression distinguishes mouse from human hematopoiesis in the basophil and erythroid lineages

E-cadherin is a key regulator of epithelial cell-cell adhesion, which loss accelerates tumor growth and invasion. Aside epithelia, E-cadherin is also expressed in hematopoietic cells. The function of hematopoietic E-cadherin is however mostly elusive. In this study, we validated mouse models for functional investigation of hematopoietic E-cadherin in human hematopoiesis. We generated a hematopoietic specific E-cadherin knockout mouse model. In mice, hematopoietic E-cadherin is predominantly expressed within the basophil lineage, which expression is dispensable for the generation of basophils. Remarkably, E-cadherin mRNA or protein were not detected in human basophils. In contrast, human hematopoietic E-cadherin marks the erythroid lineage. E-cadherin expression in hematopoiesis thereby revealed striking evolutionary differences within the basophil and erythroid cell lineage between human and mouse. This is remarkable as E-cadherin expression in epithelia is highly conserved among vertebrates including human and mouse. Our study therefore revealed that the mouse does not represent a suitable model to study the function of E-cadherin in human hematopoiesis. Mouse models can be used to define the role of E-cadherin in basophils, which regulation however may not be conserved in human basophils. Overall, our study underscores the need to develop alternative means to study the role of E-cadherin in human erythropoiesis. Overall design: E-cadherin+;cKIT+ and Ecadherin+;cKIT- isolated from mouse (FVB) bone marrow were sorted and used at a 2x single cell suspension at final conc. 1000 cells/µl in 1xPBS containing 0.04% weight/volume BSA (400 µg/ml). Cells were loaded into a 10X Genomics_Chromium_Controller for capture and barcoding following the 10X Genomics Protocol (Chromium Single Cell 3' Reagent Kits v3, CG000183 Rev A), as described by the manufacturer (10X Genomics).