Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA975959 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24728113.fastq.gz | Fastqsanger.gz | |||
| SRR24728114.fastq.gz | Fastqsanger.gz | |||
| SRR24728115.fastq.gz | Fastqsanger.gz | |||
| SRR24728116.fastq.gz | Fastqsanger.gz | |||
| SRR24728117.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Scribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members appear to be conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1. Despite its reported suppressive function in HSC self-renewal, inactivation of LLGL1 in AML confirms its relevant role for proliferative capacity and development of AML. Its function was conserved in human and murine models of AML and across various genetic backgrounds. Loss of LLGL1 results in loss of stemness-associated gene-expression including HoxA-genes and induces a GMP-like phenotype in leukemic cells. Finally, re-expression of HoxA9 facilitates functional and phenotypic rescue. Collectively, these data establish LLGL1 as a specific dependency and putative target in AML and emphasizes its cell-type specific functions.
2023-08-03 | GSE233381 | GEO
Project description:Oncogenic mutations confer aberrant replicative capacity to cells with little or no replicative capacity, generating cancer stem cells that perpetuate the tumor through extensive self-replication and differentiation blockade. However, whether oncogenes disrupt the cellular identity ofcancer stem cell by altering the developmental potential is unknown. Fate conversion has been demonstrated by ectopic expression of master transcriptional regulators, such as PU.1 and C/EBP alpha that confers myeloid cell fate to other cell types, and PRDM16 that confers brown adipose fate to white adipocytes or myoblasts. Here we show that a transcriptional regulator overexpressed in human myeloid malignancies, PRDM16s, causes oncogenic fate conversion, by transforming cells fated to form platelets and erythrocytes into myeloid leukemia-initiating cells (LICs). Prdm16s expression in hematopoietic progenitor cells caused a myelodysplastic syndrome (MDS)-like disease that progressed to acute myelogenous leukemia (AML). The myeloid diseases caused by Prdm16s exhibited expansion of megakaryocyte-erythroid progenitors (MEPs) but not granulocyte-macrophage progenitors. MEPs from Prdm16s-induced leukemia possessed LIC potential, and expression of Prdm16s in normal MEPs was sufficient to convert them to myeloid LICs and blocked megakaryocytic/erythroid potential. Prdm16s induced the expression of myeloid master regulators, including PU.1 and C/EBP alpha, by interacting with their super enhancers. Ablation of myeloid master regulators attenuated the myeloid potential and reinstalled the megakaryocytic/erythroid potential of leukemic-MEPs in mouse models and in human AML with PRDM16 rearrangement. Our study demonstrates that oncogenic Prdm16 expression converts the fate of MEPs to a malignant myeloid fate by activating myeloid master transcription factors.
| EGAS00001003235 | EGA
Project description:ZGLP1 is a determinant for the oogenic fate in mice
| PRJNA511429 | ENA
Project description:Calpains are non-lysosomal, Ca2+-dependent cysteine proteases, which are associated with various cellular functions but have so far been mainly studied in the context of disease. Their contribution to homeostasis in the healthy organism is still not well understood and their substrates have remained enigmatic in most cases. In the present study, we describe a previously unrecognized role for the calpain protease calpain2 in the regulation of neuronal differentiation of adult neural stem- and progenitor cells through cleavage and elimintation of the neuronal fate determinant MEIS2. Mass spectrometry analysis was performed on immunoprecipitated MEIS2 protein to identify phosphory¬lated residues in MEIS2 and on immunoprecipitated MEIS2 incubated with native porcine calpain2 to map calpain2-induced cleavage sites in the protein.
2024-02-08 | PXD036442 | Pride
Project description:Metabolic characteristics of adult stem cells are distinct from their differentiated progeny, and cellular metabolism is emerging as a potential driver of cell fate conversions. However, how metabolism influences fate determination remains unclear. Here, we identified inherited metabolism imposed by functionally distinct mitochondrial age-classes as a fate determinant in asymmetric division of epithelial stem-like cells. While chronologically old mitochondria support oxidative respiration, new organelles are immature and metabolically less active. Upon cell division, selectively segregated mitochondrial age-classes elicit a metabolic bias in progeny cells, with old mitochondria imposing oxidative energy metabolism inducing differentiation. High pentose phosphate pathway flux, promoting redox maintenance, is favoured in cells receiving newly synthesised mitochondria, and is required to maintain stemness during early fate determination after division. Our results demonstrate that fate decisions are susceptible to intrinsic metabolic bias imposed by selectively inherited mitochondria.
2021-12-20 | PXD010667 | Pride
Project description:Despite recent advances in the identification of lymphoid-restricted progenitors, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected role for the myeloid oncogene Mef2c in multipotent progenitors (MPPs), where it is required for pan-lymphoid differentiation. Mef2c deficiency was associated with profound defects in B, T, NK cell and common lymphoid progenitor production and an enhanced myeloid output. Mef2c deficiency in MPPs leads to downregulation of several key lymphoid regulators and the upregulation of the myeloid factor C/EBPa. Our studies also show that Mef2c is a critical transcriptional target of PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates lymphoid specification and cell fate choice in MPPs.
2008-11-21 | GSE13686 | GEO
Project description:Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway. Preventing K10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. K10 knockdown induced expression of the nuclear receptor subfamily 4, group A, member 1 (NR4A1) and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels and increased LAMP2 expression. We therefore describe a novel drug-able pathway whereby MDM2 ubiquitinates and degrades K10 increasing NR4A1 expression allowing VZV replication and propagation.
2019-08-29 | GSE136586 | GEO
Project description:STAT5 tetramerization is a central determinant of monocyte fate and colonic pathogenicity
| PRJNA856666 | ENA
Project description:ZGLP1 is a determinant for the oogenic fate in mice (RNA-seq)
| PRJNA511431 | ENA