Exosc8-Regulated Genes in Fetal Liver-Derived Erythroid Progenitor Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60136 | GEO | 2014/08/09
SECONDARY ACCESSION(S): PRJNA257836
REPOSITORIES: GEO
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Project description:Exosc8 and Exosc9 are components of the exosome that establish a barricade to erythroid maturation. Here, we knocked down Exosc8 in fetal liver-derived erythroid progenitor cells to determine the cohort of Exosc8-regulated genes in erythroid cells. Freshly isolated fetal liver progenitor cells were infected with retrovirus expressing shRNA targeting either luciferase or Exosc8. Total RNA was isolated from these cells after 3 days ex-vivo culture, during which the cells underwent erythroid maturation.
2014-08-09 | E-GEOD-60136 | biostudies-arrayexpress
Project description:We used scRNAseq to profile CD71/CD24low fetal liver erythroid progenitor cells isolated by 2 distinct methods: FACS and immunomagnetic isolation. Cells from both isolation methods were hashtagged using Biolegend mouse hashtag antibodies and library prepped together on the 10X chromium platform with the 3'RNA v3 kit. We also performed CITE-seq to profile proteogenomic expression of CD117 and CD71 on lineage-depleted mouse fetal liver erythroid progenitor cells. CITE-seq was performed through a separate library prep on the 10X chromium platform with the 3'RNAv3 kit.
2021-11-12 | GSE188287 | GEO
Project description:scRNAseq of isolated fetal liver erythroid progenitor cell subpopulations, and CITE-seq of mouse fetal liver erythroid progenitors
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Project description:Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that the human exosome maintains progenitor cell function. The expression of several subunits of the exosome were found to be enriched in epidermal progenitor cells, which were required to retain proliferative capacity and to prevent premature differentiation. Loss of PM/Scl-75 also known as EXOSC9, a key subunit of the exosome complex, resulted in loss of cells from the progenitor cell compartment, premature differentiation, and loss of epidermal tissue. EXOSC9 promotes self-renewal and prevents premature differentiation by maintaining transcript levels of a transcription factor necessary for epidermal differentiation, GRHL3, at low levels through mRNA degradation. These data demonstrate that control of differentiation specific transcription factors through mRNA degradation is required for progenitor cell maintenance in mammalian tissue. Refer to publication (Mistry et. Cell Stem Cell 2012) for more detail For gene expression profiling, cultured primary human keratinocytes were knocked down for EXOSC9, EXOSC9 and GRHL3, or control. RNA was harvested from the cells 5 days after knockdown. Microarray analysis using Affymetrix HG-U133 2.0 plus arrays was performed on duplicate samples. Significantly changed genes were identified as previously described(Sen et al., 2010).
2012-04-27 | E-GEOD-37637 | biostudies-arrayexpress
Project description:Advances in sequencing-based genomic profiling present a new challenge of explaining how changes in DNA/RNA are translated into proteins linking genotypes to phenotypes. The developing erythroid cells require highly coordinated gene expression and metabolism, and serve as a unique model in dissecting regulatory events in development and disease. Here we compare the proteomic and transcriptomic changes in human hematopoietic stem/progenitor cells and lineage-committed erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Two principal mitochondrial factors TFAM and PHB2 are tightly regulated at the protein level and indispensable for mitochondria and erythropoiesis. mTORC1 signaling is progressively enhanced to promote translation of mitochondrial proteins during erythroid specification. Genetic and pharmacological perturbation of mTORC1 or mitochondria impairs erythropoiesis. Our studies suggest a new mechanism for regulation of mitochondrial biogenesis through mTORC1-mediated protein translation, and may have direct relevance to the hematological defects associated with mitochondrial diseases and aging. Transcriptional profiling in human primary fetal and adult CD34+ hematopoietic stem/progenitor cells (HSPCs) erythroid progenitor cells (ProEs) by RNA-seq analysis.
2017-05-15 | E-GEOD-74053 | biostudies-arrayexpress
Project description:Gene expression profiling was performed on primary human erythroid progenitor cells left untreated or treated with 0.5uM SAHA. The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a novel bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease. Gene expression profiling was performed on primary human erythroid progenitor cells left untreated (n=3) or treated with 0.5uM SAHA (n=3).
2010-07-29 | E-GEOD-22367 | biostudies-arrayexpress
Project description:Gene expression profiling was performed on primary human erythroid progenitor cells left untreated or treated with 2uM NK57 for 3 days. The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a novel bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease. Gene expression profiling was performed on primary human erythroid progenitor cells left untreated (n=7) or treated with 2uM NK57 for 3 days (n=2).
2010-07-29 | E-GEOD-22368 | biostudies-arrayexpress
Project description:Ter-119 is a better murine erythroid selection marker than CD71 for bulk immunomics, murine bone marrow and fetal liver erythroid cells have different antimicrobial immune transcriptome signatures, murine bone marrow erythropoiesis is comprised of two branches In this study, we decided to benchmark erythroid cells’ selection and enrichment markers – CD71 and Ter-119 via bulk immune transcriptomics by Nanostring and perform bulk immune transcriptome profiling of Ter-119+ erythroid cells from the bone marrow and the fetal liver by Nanostring.
2023-07-31 | GSE238190 | GEO
Project description:Expression profiling of fetal liver erythroid precursors after either Hipk1 or Hipk2 knockdown by shRNA versus control shRNA
2009-07-16 | GSE17106 | GEO
Project description:Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins). Abstract (submitted paper): rationale for expression profiling Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic developmentâbecause Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferationâexplained in part by impaired cell cycle progression as well as increased apoptosisâand terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesisâsuch as alpha-globin and mitoferrin 1âdemonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.
2010-07-08 | E-GEOD-20391 | biostudies-arrayexpress