PT  - JOURNAL ARTICLE
AU  - Wanet, Anaïs
AU  - Bassal, Mahmoud A.
AU  - Patel, Sweta B.
AU  - Marchi, Francisco
AU  - Mariani, Samanta A.
AU  - Ahmed, Nouraiz
AU  - Zhang, Haoran
AU  - Borchiellini, Marta
AU  - Chen, Sisi
AU  - Zhang, Junyan
AU  - Di Ruscio, Annalisa
AU  - Miyake, Kensuke
AU  - Tsai, Mindy
AU  - Paranjape, Anuya
AU  - Park, Shin-Young
AU  - Karasuyama, Hajime
AU  - Schroeder, Timm
AU  - Dzierzak, Elaine
AU  - Galli, Stephen J.
AU  - Tenen, Daniel G.
AU  - Welner, Robert S.
TI  - E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates
AID  - 10.1126/sciimmunol.aba0178
DP  - 2021 Feb 05
TA  - Science Immunology
PG  - eaba0178
VI  - 6
IP  - 56
4099  - http://immunology.sciencemag.org/content/6/56/eaba0178.short
4100  - http://immunology.sciencemag.org/content/6/56/eaba0178.full
SO  - Sci. Immunol.2021 Feb 05; 6
AB  - 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.