The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification
(2019) In Frontiers in Immunology 10.- Abstract
The apparition of adaptive immunity in Gnathostomata correlates 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 Common lymphoid precursors (CLPs) and a near complete block in B-cell development. In the thymus, Early T-cell progenitors (ETPs) were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, hematopoietic stem cells (HSCs), erythro-myeloid progenitors, and innate immune cells were... (More)
The apparition of adaptive immunity in Gnathostomata correlates 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 Common lymphoid precursors (CLPs) and a near complete block in B-cell development. In the thymus, Early T-cell progenitors (ETPs) were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, hematopoietic stem cells (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 full Gnathostomata E-protein repertoire was critical to reinforce the gene regulatory circuits that drove the emergence and expansion of the lineages constituting humoral immunity.
(Less)
- author
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- E-protein, evolution, hematopoiesis, humoral immunity, lymphoid specification
- in
- Frontiers in Immunology
- volume
- 10
- article number
- 455
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85064190953
- pmid:30936870
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2019.00455
- language
- English
- LU publication?
- yes
- id
- 55c6358c-24c2-4273-a01b-9f588d0dd870
- date added to LUP
- 2019-05-02 14:53:35
- date last changed
- 2024-09-17 18:33:45
@article{55c6358c-24c2-4273-a01b-9f588d0dd870, abstract = {{<p>The apparition of adaptive immunity in Gnathostomata correlates 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 Common lymphoid precursors (CLPs) and a near complete block in B-cell development. In the thymus, Early T-cell progenitors (ETPs) were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, hematopoietic stem cells (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 full Gnathostomata E-protein repertoire was critical to reinforce the gene regulatory circuits that drove the emergence and expansion of the lineages constituting humoral immunity.</p>}}, author = {{Bouderlique, Thibault and Peña-Pérez, Lucia and Kharazi, Shabnam and Hils, Miriam and Li, Xiaoze and Krstic, Aleksandra and De Paepe, Ayla and Schachtrup, Christian and Gustafsson, Charlotte and Holmberg, Dan and Schachtrup, Kristina and Månsson, Robert}}, issn = {{1664-3224}}, keywords = {{E-protein; evolution; hematopoiesis; humoral immunity; lymphoid specification}}, language = {{eng}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification}}, url = {{http://dx.doi.org/10.3389/fimmu.2019.00455}}, doi = {{10.3389/fimmu.2019.00455}}, volume = {{10}}, year = {{2019}}, }