Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PRL2 deficiency alters FLT3 mediated gene transcription in murine hematopoietic stem and progenitor cells

ABSTRACT: To gain insights into the molecular mechanisms underlying the role of PRL2 in hematopoietic stem and progenitor cells (HSPCs), we performed RNA-seq analysis to compare gene expression in Prl2+/+ and Prl2-/- fetal liver cells which are enrich with HSPCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE208136 | GEO | 2022/07/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth

Project description:Fetal hematopoietic stem and progenitor cells (HSPCs) migrate from fetal liver (FL) to bone marrow (BM) around birth. While adult BM HSPCs and their extrinsic regulation is well studied, little is known about the composition, function, and extrinsic regulation of the first HSPCs to enter the BM. Here, we show that HSPCs colonize multiple fetal bones by E15.5, shift from an MPP2 to an MPP3/4-dominant phenotype by birth, and display little function until E18.5, relative to their FL counterparts. We establish a transcriptional atlas of single perinatal HSPCs, and their putative BM niches, from E15.5 through P0 and show that early fetal BM (FBM) lacks HSPCs with intrinsic stem cell programs and niche cells supportive of HSPCs. In contrast, stem cell programs are preserved in neonatal BM HSPCs, which engage with a niche expressing HSC supportive factors distinct from those seen in adult BM (i.e., IGF).

2021-06-26 | GSE178951 | GEO

Expression Profiling of Primary Human Fetal and Adult Hematopoietic Stem/Progenitor Cells (HSPCs) and Differentiating Proerythroblasts (ProEs)

Project description:To facilitate comparative genomic analyses of human fetal and adult cells undergoing erythropoiesis, we employed a serum-free two-phase liquid culture system to expand and differentiate primary human CD34+ hematopoietic stem/progenitor cells (HSPCs) ex vivo. In this experimental context, highly enriched populations of stage-matched, differentiating, primary proerythroblasts (ProEs) were generated. We selected four time points (day 0, CD34+ HSPCs; day 3, 5, and 7, differentiating ProEs) that represented similar stages differentiation for gene expression profiling using microarrays. Primary maturing fetal or adult erythroblasts were generated ex vivo from CD34+ hematopoietic stem/progenitor cells (HSPCs) using a serum-free two-phase liquid culture system. Total RNA from primary fetal and adult HSPCs (day 0) and differentiating proerythroblasts (ProEs; day 3, 5, and 7) were extracted and used to hybridize to Affymetrix expression arrays using the HG-U133 Plus 2.0 platform.

2012-10-05 | E-GEOD-36984 | biostudies-arrayexpress

Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring

Project description:Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to the increasing prevalence of these diseases yet the mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, and functional levels in bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring and in hematopoietic stem and progenitor cells (HSPCs) from fetal and juvenile bone marrow and fetal liver. mWSD exposure is also associated with increased oleic acid in fetal and juvenile bone marrow and fetal liver. ATAC-seq profiling of HSPCs and BMDMs from mWSD-exposed juveniles supports a model in which HSPCs transmit pro-inflammatory memory to myeloid cells beginning in utero. These findings demonstrate that maternal diet alters long-term immune cell developmental programming in HSPCs with proposed consequences for chronic diseases featuring altered immune/inflammatory activation across the lifespan.

2023-03-13 | GSE219095 | GEO

Runx1 deficiency decreases ribosome biogenesis and confers stress resistance to hematopoietic stem and progenitor cells

Project description:The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating pre-leukemic stem cells that expand in the bone marrow. Here we show that, counter-intuitively, Runx1 deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involves decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins, and binds the ribosomal DNA repeats. Runx1 deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and endoplasmic reticulum stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1 deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs. Comparison of the phenotypic and molecular properties of normal (Runx1f/f, or WT) versus Runx1 deficient (Mut) hematopoietic stem cells.

2015-07-27 | E-GEOD-67609 | biostudies-arrayexpress

PRL2 deficiency alters FLT3 mediated gene transcription in murine hematopoietic stem and progenitor cells

Project description:PRL2 deficiency alters FLT3 mediated gene transcription in murine hematopoietic stem and progenitor cells

| PRJNA858450 | ENA

Quantitative Proteomic Analysis of Mouse Fetal and Adult Hematopoietic Progenitor Cells

Project description:Quantitative proteomic analysis of mouse fetal and adult hematopoietic progenitor cells using TMT6plex and an SPS-MS3 method.

2020-07-02 | MSV000085672 | MassIVE

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

Unravelling human hematopoietic progenitor cell diversity through association with intrinsic regulatory factors

Project description:Hematopoietic stem and progenitor cell (HSPC) transplantation is an essential therapy for the treatment of hematological conditions, but finer definitions of human HSPC subsets with associated function could enable better tuning of grafts and more routine application in patients with lower risks. To deeply characterize human HSPCs, we quantified 41 surface proteins and functional regulators on millions of CD34+ and CD34- cells, spanning four primary human hematopoietic tissues: bone marrow, mobilized peripheral blood, cord blood, and fetal liver. We propose more granular definitions of HSPC subsets and provide new, detailed differentiation trajectories of erythroid and myeloid lineages. These aspects of our revised human hematopoietic model were validated with corresponding epigenetic analysis and in vitro clonal differentiation assays. Overall, we demonstrate the utility of using molecular regulators as surrogates for cellular identity and functional potential, providing a framework for description, prospective isolation, and cross-tissue comparison of HSPCs in humans.

2023-08-20 | GSE241229 | GEO

Normal hematopoietic stem and progenitor cells in murine acute myeloid leukemia model in vivo

Project description:Bone marrow inflammation has been linked to acute myeloid leukemia (AML) progression. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche, but the involvment of normal hematopoietic stem and progenitor cells (HSPCs) in the inflammatory crosstalk is not well understood. To better model compartmental inflammation in AML, we first established a highly penetrant, immunocompetent, fully congenic system. Using the monoblastic AML cell line C1498 (CD45.2+), we grafted non-condition C57BL/6J (CD45.1) mice, avoiding changes in BM niche function. We then fluoresence-activated cell sorting (FACS)-sorted residual normal HSPCs for single-cell RNA-sequencing analysis. We show that residual normal HSPCs from C1498-grafted mice expresses key inflammatory signature and are enriched in inflammatory signaling related pathways. Overall, we show that normal HSPCs engages in inflammatory signaling in AML niche.

2024-01-01 | GSE238091 | GEO

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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