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The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification

Bouderlique, Thibault ; Peña-Pérez, Lucia ; Kharazi, Shabnam ; Hils, Miriam ; Li, Xiaoze ; Krstic, Aleksandra ; De Paepe, Ayla ; Schachtrup, Christian ; Gustafsson, Charlotte and Holmberg, Dan LU , et al. (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.

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organization
publishing date
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
2024-05-15 05:18:59
@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}},
}