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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE211102 | GEO | 2022/11/15

REPOSITORIES: GEO

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E-cadherin marks the early commitment of murine hematopoietic progenitors to the basophil and mast cell fate

Project description:E-cadherin is a calcium-dependent cell-cell adhesion molecule extensively studied for its involvement in tissue formation, epithelial cell behavior and suppression of cancer; however its expression in the hematopoietic system hasn't received much attention. Combining single-cell RNA sequencing analyses and immunophenotyping, we revealed expression of E-cadherin in the basophil and mast cell lineages. No defect in basophil and mast cell differentiation was observed in mice lacking E-cadherin in the hematopoietic system, supporting that E-cadherin is not required per se for basophil and mast cell differentiation. Yet, we evidenced that granulocyte-monocyte progenitors expressing high levels of E-cadherin have an enriched capacity to differentiate into basophils and mast cells. Importantly, E-cadherin expression is observed on committed progenitors prior to the expression of other reported markers of these lineages. We named those progenitors pro-BMPs (pro- basophil and mast cells progenitors). Using RNA-sequencing, we demonstrated the transcriptional priming of pro-BMPs to the basophil and mast cell lineages.

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