Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NFIC overexpression perturbs normal haematopoeisis by promoting myeloid differentiaon

ABSTRACT: Nuclear factor I-C belongs to a family of CTF binding transcription factor which is known for its role cellular differentiation. In our recent study we identified increased expression of NFIC in. AML samples as compared to normal haematpoitic stem and progenitor cells (HSPCs). We also found that overexpression of NFIC in cord blood derived HSPCs perturbed normal haematopoiesis by increasing monocyte production. Therefore in this analysis we aimed to identify the effect of NFIC overexpression in normal HSPCs at single cell level using single cell RNA (scRNA) sequencing. Cluster analysis based on the cellular and functional identities, identified eight clusters according to their terminal differentiation as monocytes, erythrocytes, dendritic cells (DC), megakaryocytes, neutrophils, megakaryocyte-erythroid progenitor cells, basophil/mast progenitor cells and eosinophils. We found that NFIC overexpressing CD34+ HSPCs had increased percentage of monocytes as compared to control. To understand the molecular basis of this, we focussed our analysis on monocytes to determine changes in mRNA expression following NFIC overexpression. We identified 164 and 88 significantly up-regulated and down-regulated genes, respectively (p<0.05, FDR<0.05) in NFIC overexpressing monocytes as compared to control. Pathway analysis identified enrichment in genes involved in mTOR signalling, cancer cell death and survival, energy metabolism pathways and oxidative phosphorylation. Therefore our scRNA suggested that NFIC play a role in monocytic growth development and its overexpression may lead to monocytic bias in normal haematopoiesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200456 | GEO | 2023/01/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Quantitative analysis of redox proteome reveals protein thiol switches regulating fundamental processes in developmental haematopoiesis

Project description:Foetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behaviour in normal and malignant haematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse foetal and adult HSPCs. We defined the redox state of 4455 cysteines in foetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in foetal HSPCs. Our data identified ontogenically active redox switches in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified redox switches acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in foetal HSPCs. Our data has demonstrated that redox signalling contributes to the regulation of fundamental processes of developmental haematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukaemia.

2022-06-09 | PXD030043 | Pride

Quantitative analysis of redox proteome reveals protein thiol switches regulating fundamental processes in developmental hematopoiesis

Project description:Fetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behaviour in normal and malignant haematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse fetal and adult HSPCs. We defined the redox state of 4455 cysteines in fetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in fetal HSPCs. Our data identified ontogenically active redox switches in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified redox switches acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in fetal HSPCs. Our data has demonstrated that redox signalling contributes to the regulation of fundamental processes of developmental hematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukaemia. An H9 human embryonic stem cells cell line was applied to validate data from the primary cells.

2022-06-09 | PXD033115 | Pride

Foetal and adult HSPCs - Comprehensive Proteomic Characterization of Ontogenic Changes in Hematopoietic Stem and Progenitor Cells

Project description:Haematopoietic stem and progenitor cells (HSPCs) in the foetus and adult possess distinct molecular landscapes that regulate cell fate and change their susceptibility to initiation and progression of haematopoietic malignancies. The proteomic programs that govern these differences remain elusive. In this study, we have utilized a mass spectrometry-based quantitative proteomics approach to comprehensively describe and compare the proteome of foetal and adult HSPCs. We found that the proteome of foetal HSPCs is relatively simple, characterized by proteins involved in cell cycle and cell proliferation, while their adult counterparts are defined by a larger set of proteins that are involved in more diverse cellular processes. These adult characteristics include an arsenal of proteins important for viral and bacterial defence, as well as protection against ROS-induced protein oxidation. Our further analyses of Type I interferon signalling shows that foetal HSPCs are sensitive to Interferon a (IFNa), which impairs their production of mature lymphoid cells, whereas stimulation with IFNa to the pregnant mother enhances the production of early progenitors from foetal HSCs. Our results provide new and important insights into the molecular landscape of foetal and adult haematopoiesis that advance our understanding of normal and malignant haematopoiesis during foetal and adult life.

2017-12-12 | PXD006876 | Pride

Functional effects of DNMT3A R882 on human haematopoietic stem and progenitor cells myeloid differentiation

Project description:This data presents the transcriptomes of bulk mature colonies derived from single human haematopoietic stem cells / multipotent progenitors (HSC/MPPs) and granulocyte macrophage progenitors (GMPs) purified from one indiviual with age related clonal haematopoisesis. The profiled colonies contain mature monocytes, as measured by conventional cell surface markers (CD14+, CD15-, GlyA-), but no other mature blood cell types. This dataset is part of a larger study, the main objective of which is to understand the functional effects conferred by somatic DNMT3A R882H mutation on human haematopoietic stem cell differentiation capacity. In clonal haematopoiesis, DNMT3A R882H and DNMT3A WT HSPCs co-exist in the same individual. We compared the transcriptional differences between mature monocytic colonies derived from DNMT3A R882H and WT HSPCs in vitro. Analysis of this dataset shows that, in this individual, DNMT3A R882H HSPCs produce less mature monocytes than their WT counterparts over the same culture time.

2023-08-28 | GSE241520 | GEO

KLF7 overexpression in HSPCs expression array

Project description:Increased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival. KLF7 overexpression in HSPCs expression array: Lin- c-Kit+ Sca-1+ cells transduced with a KLF7 expressing or control (empty vector) lentivirus. Expression profiles of KLF7 overexpressing vs controls HSPCs. Cells were harvested 72 hrs post-transduction to compare expression profiles of control vs KLF7 overexpressing HSPCs

2012-08-24 | E-GEOD-40327 | biostudies-arrayexpress

Effect of Jmjd6 knockout on gene expression and mRNA splicing in Lin-Sca+Kit+ haematopoietic cells

Project description:The 2-oxoglutarate dependent protein JMJD6 acts as a lysyl hydroxylase on specific residues of the splicing factor U2AF2. To understand the molecular roles of JMJD6 in normal haematopoiesis and identify any role of JMJD6 in splicing, we performed RNA-sequencing on Lin-Sca1+Kit+ (LSK) haematopoietic stem and progenitor cells (HSPCs) derived from young mice.

2021-03-05 | GSE168283 | GEO

Global miRNA expression status of human hematopoietic stem–progenitor cells modulates myelopoiesis

Project description:We investigated how suppression of the most upstream microRNA–processing RNase, Drosha, affects the differentiation of human CD34+ hematopoietic stem–progenitor cells (HSPCs). We hypothesized that knock-down of Drosha would alter blood lineage development by modulating the expression of microRNAs. Lentiviral delivery to HSPCs of a short-hairpin targeting Drosha resulted in a viable phenotype with promotion of myeloid, and especially monocytic, maturation and suppression of apoptosis. Our results show that Drosha deficiency triggered a parallel upregulation of components of the RNAi machinery, including DGCR8, Dicer and Ago2. Deep sequencing analyses revealed global miRNA deficiency after Drosha short-hairpin treatment with relative maintenance of mature miR-223 expression. Restoration of miR-223 to normal levels after Drosha knock-down further enhanced monocytic maturation concomitant with the modulation of myeloid transcription factors that promoted monocytic differentiation. Our results support a miRNA accentuation model in which relative enhancement of miR-223 increases levels of PU.1 thereby promoting monocytic differentiation. CD34+ HSPCs were isolated from umbilical cord blood and transduced with an empty lentivector (EV) or a lentivector encoding a short-hairpin RNA targeting the pri-miRNA–processing enzyme, Drosha (shDrosha). EV and shDrosha transduced HSPCs were grown in liquid culture promoting myelopoiesis and sampled on days 0 and 7 for total RNA collection. Total RNA was size fractionated to enrich for the small RNA population and deep sequenced using ABI's SOLiD 4.0 platform.

2013-12-31 | E-GEOD-47519 | biostudies-arrayexpress

Global miRNA expression status of human hematopoietic stem–progenitor cells modulates myelopoiesis

2013-12-31 | GSE47519 | GEO

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [methylation array]

Project description:Ageing is associated with an abnormal increase of DNA methylation in human gene promoters, including in the bone marrow stem cells. DNA methylation patterns are further perturbed in haematological malignancies such as acute myeloid leukaemia (AML) but the physiological significance of such epigenetic changes is unknown. Using epigenetic editing of human stem/progenitor cells (HSPCs), we show evidence that p15 methylation affects haematopoiesis in vivo. We edited the CDKN2B (p15) promoter and ARF (p14) using dCas9-3A3L and observed DNA methylation spreading beyond the location of the gRNA. We find that despite a transient delivery system, DNA methylation is maintained during myeloid differentiation in vitro, and hypermethylation of the p15 promoter reduces gene expression. In vivo, edited human HSPCs can engraft the bone marrow of mice and targeted DNA methylation is maintained in HSPCs long term. Moreover, we identified how the epigenetic changes are conserved and inherited in both myeloid and lymphoid lineages. Although the proportion of myeloid (CD33+) and lymphoid (CD19+) cells is unaffected, monocyte (CD14+) populations decreased and granulocytes (CD66b+) increased in mice engrafted with p15 hypermethylated cells. We also observe significant changes in the proportions of multipotent and committed progenitor cells. This may have clinical relevance since we found that p15 promoter methylation is present in the peripheral blood of patients with clonal haematopoiesis. Our study shows DNA methylation can be targeted and maintained in human HSPCs and demonstrated functional relevance of aberrant DNA methylation on the p15 locus. As such, other ageing associated aberrant DNA methylation may impact haematopoiesis in vivo.

2023-08-30 | GSE222178 | GEO

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [Targeted BS-seq]

2023-08-30 | GSE222179 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data