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

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Science Immunology  05 Feb 2021:
Vol. 6, Issue 56, eaba0178
DOI: 10.1126/sciimmunol.aba0178

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Basophil lineage commitment

Basophils and mast cells are innate myeloid cells involved in IgE-mediated immediate hypersensitivity reactions, but identification of committed progenitors for these cell types has been challenging. Wanet et al. used gene expression data from hematopoietic progenitors in mice to identify E-cadherin as a candidate marker associated with early basophil/mast cell progenitors and present on some cells on which the high-affinity IgE receptor (FcεRIα) was not yet detected. E-cadherin expression in these progenitors was directly regulated by the GATA-2 transcription factor. Combining E-cadherin and the mature basophil marker CD49b will offer a technique for selecting mature basophils for functional studies while leaving FcεRIα untouched. These studies provide further insights into how hematopoietic progenitors commit to differentiate into basophils or mast cells.


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.

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