The concerted action of E2-2 and HEB is critical for early lymphoid specification
| Autor: | Lucía Peña-Pérez, Xiaoze Li, Robert Månsson, Miriam Hils, Aleksandra Krstic, Ayla De Paepe, Thibault Bouderlique, Christian Schachtrup, Charlotte Gustafsson, Shabnam Kharazi, Kristina Schachtrup, Dan Holmberg |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mice Transcription Factor 4 0302 clinical medicine humoral immunity Gene Duplication Basic Helix-Loop-Helix Transcription Factors Immunology and Allergy Phylogeny Original Research 0303 health sciences biology Repertoire 030302 biochemistry & molecular biology lymphoid specification Lymphoid Progenitor Cells Acquired immune system Biological Evolution Cell biology Haematopoiesis Multigene Family Vertebrates Stem cell lcsh:Immunologic diseases. Allergy Immunology Evolution Molecular 03 medical and health sciences evolution Animals Cell Lineage Amino Acid Sequence Progenitor cell E-protein Gene 030304 developmental biology Innate immune system Sequence Homology Amino Acid Gnathostomata Hematopoietic Stem Cells biology.organism_classification hematopoiesis Lymphocyte Subsets Immunity Humoral Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Humoral immunity Leukopoiesis lcsh:RC581-607 Sequence Alignment Spleen 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
| DOI: | 10.1101/465765 |
| Popis: | The apparition of adaptive immunity inGnathostomatacorrelates with the expansion of the E-protein family to encompass E2-2, HEB and E2A. Within the family, E2-2 and HEB are more closely evolutionarily related but their concerted action in hematopoiesis remains to be explored. Here we show that the combined disruption of E2-2 and HEB results in failure to express the early lymphoid program in CLPs and a near complete block in B-cell development. In the thymus, ETPs were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, HSCs, erythro-myeloid progenitors and innate immune cells were unaffected showing that E2-2 and HEB are dispensable for the ancestral hematopoietic lineages. Taken together, this E-protein dependence suggests that the appearance of the fullGnathostomataE-protein repertoire was critical to reinforce the gene regulatory circuits that drove the emergence and expansion of the lineages constituting humoral immunity. |
| Databáze: | OpenAIRE |
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