Research ArticleMYELOID CELL DIFFERENTIATION

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

See allHide authors and affiliations

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

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

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.

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.

View Full Text

Stay Connected to Science Immunology