Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-transcription factor reporter mice delineate early precursors to the LTi and ILC lineages

ABSTRACT: Transcription factor (TF) reporter mice have proved integral to the characterization of murine innate lymphoid cell (ILC) development and function. Here, we implemented a CRISPR/Cas9-generated combinatorial reporter approach for the simultaneous resolution of several key TFs throughout ILC development in both the fetal liver and adult bone marrow. We demonstrate that the Tcf7-expressing early innate lymphoid progenitor (EILP) and the common helper innate lymphoid progenitor (CHILP) both contain a heterogeneous mixture of committed ILC and Lymphoid Tissue-inducer (LTi) precursors, rather than a shared precursor to these lineages. Moreover, the earliest specified precursor to the LTi lineage was identified upstream of these populations, prior to the expression of Tcf7. These findings match dynamic changes in chromatin accessibility associated with the expression of key TFs (ie. Gata3 and Rorc), highlighting the distinct origins of ILC and LTi lineages at the epigenetic and functional levels, and provide a revised map for ILC development.

ORGANISM(S): Mus musculus

PROVIDER: GSE150763 | GEO | 2020/09/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell analysis defines the divergence between the innate lymphoid cell and lymphoid tissue inducer lineages

Project description:The precise lineage relationships between innate lymphoid cells (ILC) and the lymphoid tissue inducer (LTi) are poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and showed that its bifurcation was precisely marked by the differential induction of the transcription factors PLZF and TCF1. Acquisition of individual ILC1/2/3-specific effector programs was initiated later, at the common ILC precursor (ILCP) stage, by transient expression of mixed ILC1/2/3 transcriptional patterns whereas, in contrast, LTi development did not go through multilineage priming. These findings provide novel insights into divergent mechanisms of ILC and LTi lineage differentiation and establish a high-resolution map of their development.

2015-12-30 | GSE76407 | GEO

Development and differentiation of early innate lymphoid progenitors

Project description:Early innate lymphoid progenitors (EILP) have recently been identified in the mouse adult bone marrow as a multipotential progenitor population committed to ILC lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor-successor relationships between EILP, IL-7R+ common lymphoid progenitors (ALP), and ILC precursors (ILCp). Bioinformatic, phenotypical, functional, and genetic approaches collectively establish EILP as an intermediate progenitor between ALP and ILCp. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.

2017-11-15 | GSE81530 | GEO

Dynamic chromatin structure during early ILC progenitor differentiation

Project description:To characterize the epigenomes during early ILC progenitor differentiation, we did DNase-seq, CUT&RUN and scMNase-seq assays in all-lymphoid progenitor (ALP), early innate lymphoid progenitor (EILP), and innate lymphoid cell progenitor (ILCP) cells.

2019-05-30 | GSE128483 | GEO

Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells

Project description:Lymphoid tissue inducer (LTi) cells are regarded as a subset of innate lymphoid cells (ILCs). However, these cells are not derived from the ILC common progenitor, which generates other ILC subsets and is defined by the expression of the transcription factor PLZF. Here we examined transcription factor(s) determining the fate of LTi progenitor versus non-LTi ILC progenitor. Conditional deletion of Gata3 resulted in the loss of PLZF+ non-LTi progenitors but not the LTi progenitors that expressed the transcription factor RORγt. Consistently, PLZF+ non-LTi progenitors expressed high amounts of GATA3 whereas GATA3 expression was low in RORγt+ LTi progenitors. The generation of both progenitors required the transcriptional regulator Id2, which defines the common helper-like innate lymphoid progenitor, but not cytokine signaling. Nevertheless, low GATA3 expression was necessary for the generation of functionally mature LTi cells. Thus, differential expression of GATA3 determines the fates and functions of distinct ILC progenitors.

2019-12-24 | GSE93863 | GEO

The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

Project description:Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of CLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6+ cells within the CLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development. This experiment is to compare gene expression profiles between wild-type and Nfil3-/- common lymphoid progenitor (CLP) cells to identify genes regulated by NFIL3. There are 6 samples in this experiment, including 3 biological replicates for wild-type CLPs and 3 biological replicates for Nfil3-/- CLPs. All mice used are on the C57BL/6 background.

2014-10-16 | E-GEOD-62337 | biostudies-arrayexpress

Early innate lymphoid cell progenitor

Project description:We identified a new type of bone marrow progenitors termed early innate lymphoid cell progenitor (EILP) using TCF-1 GFP reporter mice. We compared the transcriptomes of early innate lymphoid cell progenitors (EILP) with other early progenitors, including HSC, LMPP, CMP, CLP, ETP and DN3.

2015-08-17 | GSE69789 | GEO

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi. The various ILC cell populations analyzed in this study were isolated from C57BL/6 RORc(gt)+/GFP reporter mice. SI NKp46+RORγt- (NKp46+GFP-) cells, SI NKp46+RORγt+ cells (NKp46+GFPlow and NKp46+GFPhigh cells) and NKp46-RORγt+ ILCs, including adult LTi cells , were sorted by flow cytometry from CD3- lamina propria cells of small intestine (SI) of RORc(γt)+/GFP reporter mice . Splenic NKp46+RORγt- (NKp46+GFP-) cells were also sorted as the reference for conventional NK cells. Two replicates of each populations were produced and analyzed.

2011-06-20 | E-GEOD-29777 | biostudies-arrayexpress

The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

2014-10-16 | GSE62337 | GEO

Distinct waves from the hemogenic endothelium give rise to layered Lymphoid Tissue Inducer cell ontogeny [bulk RNA-seq]

Project description:LTi cells are part of the ILC family and essential for the formation of secondary lymph nodes within the embryo. This data set contains the analysis of lymphoid tissue (LTi) cell ontogeny, studied by expression profile analysis with RNA bulk sequencing of the populations associated with LTi ontogeny isolated from fetal liver vs. embryonic periphery at embryonic stage E13.5. They indicate a proliferating precursor population mainly in the fetal liver, while the embryonic periphery harbors the definitive lineage.

2020-08-01 | GSE153607 | GEO

Gene expression analysis of CD4+ and CD4- ILC1 subsets by RNAseq

Project description:Innate lymphoid cell (ILC) subsets that mirror helper T cells in their effector cytokine profiles have recently emerged as central players in both homeostatic and inflammatory conditions. Like their Th1, Th2 and Th17/Th22 helper T cell counterparts, ILC subsets are categorized based on their expression of specific transcription factors and effector cytokines: group 1 ILC (ILC1) express T-bet and IFN-Î³; group 2 ILC (ILC2) express GATA-3 and type 2 effector cytokines such as IL-13 and IL-5; and group 3 ILC (ILC3) express RORgt and the cytokines IL-22 and/or IL-17. Under this nomenclature, natural killer (NK) cells and lymphoid tissue inducers (LTi) are considered ILC1 and ILC3, respectively. ILC1 contain both CD4+ and CD4- populations, but whether this phenotypic characteristic reflects functional differences between these two populations is unknown. These studies examine the gene expression profiles of CD4+ vs CD4- ILC1 in a cohort of healthy control subjects. ILC subsets were isolated from the peripheral blood of healthy control subjects. cDNA was isolated and amplified from sorted populations, and gene expression was analyzed by RNAseq

2015-12-31 | E-GEOD-69596 | biostudies-arrayexpress

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