E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates
- 12 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 6 (56)
- https://doi.org/10.1126/sciimmunol.aba0178
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.Keywords
Funding Information
- NIH Office of the Director (P01HL131477)
- NIH Office of the Director (5P01CA66996)
- NIH Office of the Director (R35CA197697)
- NIH Office of the Director (P01HL095489)
- NIH Office of the Director (R01AR067145)
- NIH Office of the Director (R01AI132494)
- NIH Office of the Director (R00CA188595)
- NIH Office of the Director (P01HL131477)
- BAEF
- WBI
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