E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates.

Science immunology 2021 Feb 05

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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. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Citation

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. E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates. Science immunology. 2021 Feb 05;6(56)