E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates
Anaïs Wanet, Mahmoud A. Bassal, Sweta B. Patel, Francisco Marchi, Samanta A. Mariani, Nouraiz Ahmed, Haoran Zhang, Marta Borchiellini, Sisi Chen, Junyan Zhang, Annalisa Di Ruscio, Kensuke Miyake, Mindy Tsai, Anuya Paranjape, Shin‐Young Park, Hajime Karasuyama, Timm Schroeder, Elaine Dzierzak, Stephen J. Galli, Daniel G. Tenen, Robert S. Welner
Abstract
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, E-cadherin expression in the hematopoietic system has not been fully elucidated. Combining single-cell RNA-sequencing analyses and immunophenotyping, we revealed that progenitors expressing high levels of E-cadherin and contained within the granulocyte-monocyte progenitors (GMPs) fraction have an enriched capacity to differentiate into basophils and mast cells. We detected E-cadherin expression on committed progenitors before the expression of other reported markers of these lineages. We named such progenitors pro-BMPs (pro-basophil and mast cell progenitors). Using RNA sequencing, we observed transcriptional priming of pro-BMPs to the basophil and mast cell lineages. We also showed that GATA-2 directly regulates E-cadherin expression in the basophil and mast cell lineages, thus providing a mechanistic connection between the expression of this cell surface marker and the basophil and mast cell fate specification.