Publications by authors named "Rogelio Aguilar"
Article Synopsis
- Haematopoietic stem cells are crucial for lifelong blood production and were studied in young and old mice to understand how these cells change with age.
- Researchers found that mouse stem cells accumulate about 45 somatic mutations per year, which is not drastically different from humans, despite their size and lifespan differences.
- The study revealed that while stem cells independently maintain their populations throughout life, aged mice showed different patterns of clonal diversity and expansion compared to humans, particularly after blood system disturbances.
Article Synopsis
- This text indicates a correction to a previously published article.
- The specific article is identified by its DOI: 10.1016/j.isci.2024.109122.
- The correction ensures that the information or data presented in the article is accurate and up to date.
DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies, including acute myeloid leukemia. An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly comutated genes in myeloid malignancies, such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ER murine model systems to study the effects of constitutively active Kras-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO).
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- Aging leads to a dominance of specific variants of hematopoietic stem cells (HSCs) in blood cell production, which may negatively impact health due to their differentiated progeny.* -
- Somatic mutations in the DNMT3A gene are linked to this clonal dominance, and interactions with high-fat diets (HFD) were studied in mice to understand their combined effects.* -
- The research found that reduced DNMT3A in the context of HFD promotes weight gain and inflammation by triggering pro-inflammatory pathways and abnormal DNA methylation during the differentiation of myeloid cells.*
Unlabelled: In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.
View Article and Find Full Text PDFIKAROS family zinc finger 1 (IKZF1) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-cell acute lymphoblastic leukemia. Due to the heterogeneity of concomitant lesions, it remains unclear how IKZF1 abnormalities directly affect cell function and therapy resistance, and whether their consideration as a prognostic indicator is valuable in improving outcome. CRISPR/Cas9 strategies were used to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of IKZF1 lesions to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment that can be linked to loss of IKAROS protein.
View Article and Find Full Text PDFTatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined.
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