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Expression data from long-term Ebf1-deficient, CD19+, Bcl2tg cells

ABSTRACT: An assessment of a role of Ebf1 in committed B lineage cells. In this study, we adopted the strategy of deleting Ebf1 after reconstitution of Rag2-/-Il2rg-/- mice and found that committed pre-B cells could be converted into T cells and ILCs upon deletion of Ebf1.

ORGANISM(S): Mus musculus

PROVIDER: GSE46349 | GEO | 2013/06/01

SECONDARY ACCESSION(S): PRJNA198863

REPOSITORIES: GEO

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Expression data from long-term Ebf1-deficient, CD19+, Bcl2tg cells

Project description:An assessment of a role of Ebf1 in committed B lineage cells. In this study, we adopted the strategy of deleting Ebf1 after reconstitution of Rag2-/-Il2rg-/- mice and found that committed pre-B cells could be converted into T cells and ILCs upon deletion of Ebf1. We used µ-arrays to gain insight into changes in gene expression of CD19+ Ebf1-deficient cells. The dataset was compared with microarray data available for different hematopoietic developmental stages (GSE15907). The complete dataset is linked below as a supplementary file.

2013-06-01 | E-GEOD-46349 | biostudies-arrayexpress

Identification and characterization of regenerative innate lymphoid cells from pluripotent stem cells [WT_ILC/R9_iILC_SmartSeq2]

Project description:We identified that synergistic and inducible expression of Runx1 and Hoxa9 in pluripotent stem cells gave rise to engraftable iHPC capable of developing into mature ILCs in the Rag2-/-Il2rg-/- recipients. We performed single-cell RNA-seq on the entire regenerative CD45.2+GFP+Lin-CD127+ R9-ILC population from the intestine of Rag2-/-Il2rg-/- recipient mice and the CD45.2+Lin-CD127+ WT-ILC population from the intestine of wild type mice (C57BL/6, CD45.2). Single-cell transcriptome illustrated the transcriptome landscape of the R9-ILCs and wild type ILCs including ILC1, ILC2 and ILC3.

2022-09-30 | GSE186777 | GEO

Identification of aceNKPs, a committed common progenitor of the ILC1 and NK cell continuum

Project description:The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC haematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution we have characterised bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC1/NK progenitors, which we call ‘aceNKPs’, are defined as lineage–Id2+IL-7Ra+CD25–a4b7–NKG2A/C/E+Bcl11b–. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-g and perforin upon IL-15 stimulation. Following reconstitution of Rag2–/–Il2rg–/– hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells (regardless of their tissue location) that cannot be clearly segregated into the traditional ILC1 and NK subsets, suggesting that group 1 ILCs constitute a dynamic continuum of ILCs that can develop from a common progenitor. In addition, aceNKP-derived ILC1/NK cells effectively ameliorate tumour burden in a model of lung metastasis where they acquired a cytotoxic NK cell phenotype. Our results identify the primary ILC1/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing.

2022-11-02 | GSE213814 | GEO

Genome-wide EBF1 occupancy in pro-B cells

Project description:EBF1 ChIP in Rag2(-/-) pro-B cells

2016-05-09 | GSE79140 | GEO

Transcriptomic analysis of femoral diaphysis and primary osteoprogenitor cells cultures from mouse strains with SHIP1 deficiency and controls

Project description:Investigation of the SHIP1 (Inpp5d)-dependent and Rag2/Il2rg-dependent transcriptional changes in bone and osteoprogenitor cells cultures from murine strains with SHIP1 deficiency (Inpp5dm1Btlr/ m1Btlr, http://www.informatics.jax.org/allele/key/65037) and controls. Specifically, transcriptomic analysis was performed from femoral diaphysis from SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+/styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype). Alternatively, osteoprogenitor cells isolated from bone marrow from the same genotypes as above were differentiated in vitro into primary osteoclasts in the presence or absence of RANKL. After 5 days, RNA was extracted from these cultures for transcriptomic analysis (n=3 for each genotype). Experimental Designs: Transcripts were analyzed in femoral diaphysis of SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype). Alternatively, transcripts were analyzed in primary osteoclast cultures from bone marrow cells isolated from SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype), which were supplemented or not with RANKL.

2024-02-21 | E-MTAB-13164 | biostudies-arrayexpress

Identification and characterization of regenerative innate lymphoid cells from pluripotent stem cells [R9_DAY7.5_10X_genomics]

Project description:We identified that synergistic and inducible expression of Runx1 and Hoxa9 in pluripotent stem cells gave rise to engraftable iHPC capable of developing into mature ILCs in the Rag2-/-Il2rg-/- recipients. The regenerative ILCs were detected in multiple tissues including intestine, lung, liver, spleen and thymus. We performed single cell RNA-seq on the sorted GFP+CD45.2+Lin- cells from the bone marrow of recipients at day 7.5 after iHPC transplantation. Single-cell transcriptome illustrated the existence of regenerative ILC-related progenitors including iLP, iILCP, iILC1/3P and iILC2P, and the cellular trajectory of regenerative ILCs development in vivo was closely resembles the natural ILCs development.

2022-09-30 | GSE186776 | GEO

Ebf1 or Pax5 Haploinsufficiency Synergizes with STAT5 Activation to Initiate Acute Lymphoblastic Leukemia

Project description:STAT5 is critical for differentiation, proliferation and survival of progenitor B cells suggesting a possible role in Acute Lymphoblastic Leukemia (ALL). Herein, we show increased expression of activated STAT5 in ALL patients, which correlates with treatment outcome. Mutations in Ebf1 and Pax5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1 but this had little affect on most EBF1 or PAX5 target genes. However, a subset of these genes was deregulated and included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL. Gene expression profiling was performed on cells isolated from lymph nodes of Stat5b-CA x Ebf1+/- and Stat5b-CA x Rag2-/- leukemic mice and pre B cells sorted from bone marrow of C57BL/6 mice and Stat5b-CA transgenic mice. 17 Samples.

2011-05-09 | E-GEOD-25645 | biostudies-arrayexpress

A comprehensive Proteomic Investigation of Ebf1 Heterozygosity in pro-B lymphocytes utilizing Data Independent Acquisition

Project description:Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both DIA (Data Independent Acquisition) and shotgun DDA (Data Dependent Acquisition) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells. Both DDA and DIA were able to reveal the downregulation of the EBF1 transcription factor in Ebf1+/- pro-B lymphocytes. Further examination of differentially expressed proteins by DIA revealed that, similar to EBF1, the expression of other B-cell lineage regulators, such as TCF3 and Pax5, is also down-regulated in Ebf1 heterozygous cells. Functional DIA analysis of differentially expressed proteins showed that EBF1 heterozygosity resulted in the deregulation of at least 8 transcription factors involved in lymphopoiesis, and to the deregulation of key proteins playing crucial roles in survival, development and differentiation of pro-B lymphocytes.

2017-12-20 | PXD008396 | Pride

Expansion of Interleukin-22-producing Innate Lymphoid Cells in Tristetraprolindeficient mice protects against Dextran Sulfate Sodium-induced Colitis

Project description:Tristetraprolin (TTP, encoded by Zfp36) is an RNA-binding protein that plays a major role in the control of inflammation. Zfp36 -/-mice spontaneously develop a complex multi-organ inflammatory syndrome that shares many features with spondyloarthritis. Herein, we show that Zfp36 -/-mice are paradoxically protected from Dextran Sulfate Sodium (DSS)-induced colitis. This effect was maintained on a Rag2 -/- background but was lost in Rag2 -/-Il2rg -/-Zfp36 -/-mice that lack innate lymphoid cells (ILCs). Furthermore, we observed a local expansion of type 3 ILCs in the lamina propria of Zfp36 -/-mice. These cells produced large amounts of Interleukin (IL)-22 and were expanded in response to systemic inflammation. Finally, we show that IL-22 contributed to protection of Zfp36 -/-mice against DSSinduced colitis but had a minor impact on their spontaneous inflammatory syndrome. Taken together, these data highlight the complex role of TTP in the control of organ-specific inflammation.

2023-08-01 | GSE236230 | GEO

Gene expression profile of EBF1-wt & EBF1-H240A

Project description:To study the function of EBF1-H240 residue, a gain-of function microarray analysis was performed by transducing Empty, Ebf1-wt and Ebf1-H240A expressing vectors into Ebf1-/- progenitor cells.

2016-11-21 | GSE87634 | GEO

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