AI Article Synopsis

  • Ahed is a newly identified gene in haematopoiesis that plays a crucial role in blood cell development, discovered through screening mutant embryonic stem cells.
  • Conditional knockout of Ahed leads to severe anemia and prenatal death, as its absence hampers the ability of haematopoietic cells to regenerate in living organisms.
  • Deletion of Ahed disrupts multiple biological pathways in adult mice and is linked to mutations found in cancer patients, highlighting its importance in both normal blood development and potential involvement in cancers.

Article Abstract

The development of haematopoiesis involves the coordinated action of numerous genes, some of which are implicated in haematological malignancies. However, the biological function of many genes remains elusive and unknown functional genes are likely to remain to be uncovered. Here, we report a previously uncharacterised gene in haematopoiesis, identified by screening mutant embryonic stem cells. The gene, 'attenuated haematopoietic development (Ahed)', encodes a nuclear protein. Conditional knockout (cKO) of Ahed results in anaemia from embryonic day 14.5 onward, leading to prenatal demise. Transplantation experiments demonstrate the incapacity of Ahed-deficient haematopoietic cells to reconstitute haematopoiesis in vivo. Employing a tamoxifen-inducible cKO model, we further reveal that Ahed deletion impairs the intrinsic capacity of haematopoietic cells in adult mice. Ahed deletion affects various pathways, and published databases present cancer patients with somatic mutations in Ahed. Collectively, our findings underscore the fundamental roles of Ahed in lifelong haematopoiesis, implicating its association with malignancies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199565PMC
http://dx.doi.org/10.1038/s41467-024-49252-7DOI Listing

Publication Analysis

Top Keywords

haematopoietic cells
8
ahed deletion
8
ahed
6
haematopoiesis
5
newly identified
4
identified gene
4
gene ahed
4
ahed plays
4
plays essential
4
essential roles
4

Similar Publications

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607).

View Article and Find Full Text PDF

Objectives: Exploiting the complete blood count (CBC) with differential (CBC-diff) for early sepsis detection has practical value for emergency department (ED) care, especially for those without obvious presentations. The objective of this study was to develop the CBC Sepsis Index (CBC-SI) that incorporates monocyte distribution width (MDW) to enhance rapid sepsis screening.

Design: A retrospective observational study.

View Article and Find Full Text PDF

Erythroleukemia, a complex myeloproliferative disorder presenting as acute or chronic, is characterized by aberrant proliferation and differentiation of erythroid cells. Although nootkatone, a sesquiterpene derived from grapefruit peel and Alaska yellow cedar, has shown anticancer activity predominantly in solid tumors, its effects in erythroleukemia remain unexplored. This study aimed to investigate the impact of nootkatone and its derivatives on erythroleukemia.

View Article and Find Full Text PDF

Cullin-5 (Cul5) coordinates assembly of cullin-RING-E3 ubiquitin (Ub) ligase (CRL) complexes that include Suppressor of Cytokine Signaling (SOCS)-box-containing proteins. The SOCS-box proteins function to recruit specific substrates to the complex for ubiquitination and degradation. In hematopoiesis, SOCS-box proteins are best known for regulating the actions of cytokines that utilize the JAK-STAT signaling pathway.

View Article and Find Full Text PDF

Aging and chronic inflammation are associated with overabundant myeloid-primed multipotent progenitors (MPPs) amongst hematopoietic stem and progenitor cells (HSPCs). While HSC differentiation bias has been considered a primary cause of myeloid bias, whether it is sufficient has not been quantitatively evaluated. Here, we analyzed bone marrow data from the IκB- (Nfkbia+/-Nfkbib-/-Nfkbie-/-) mouse model of inflammation with elevated NFκB activity, which shows increased myeloid-biased MPPs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!