Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA266980 | ENA |
REPOSITORIES: ENA
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Project description:Group 3 innate lymphoid cells (ILC3) are defined by the expression of RORγt, which is selectively required for their development. The lineage-specified progenitor cells of human ILC3 and their developmental site after birth remain undefined. Here we identified a novel population of human CD34+ hematopoietic progenitor cells (HPC) expressing RORγt and sharing with ILC3 a distinct transcriptional signature. RORγt+ CD34+ HPC were located in tonsils and intestinal lamina propria (LP) and selectively differentiated towards ILC3. Conversely, RORγt- CD34+ HPC displayed commitment potential for both ILC3 and NK cells and the differentiation fate towards these two cell lineages was determined by cytokine and aryl hydrocarbon receptor (AhR) signaling. Thus, we propose that RORγt+ CD34+ cells represent human lineage-specified progenitors of IL-22+ ILC3 and that tonsils as well as intestinal LP might be preferential sites of their differentiation.
2014-11-25 | GSE63197 | GEO
Project description:Group 3 innate lymphoid cells (ILC3) are defined by the expression of RORM-NM-3t, which is selectively required for their development. The lineage-specified progenitor cells of human ILC3 and their developmental site after birth remain undefined. Here we identified a novel population of human CD34+ hematopoietic progenitor cells (HPC) expressing RORM-NM-3t and sharing with ILC3 a distinct transcriptional signature. RORM-NM-3t+ CD34+ HPC were located in tonsils and intestinal lamina propria (LP) and selectively differentiated towards ILC3. Conversely, RORM-NM-3t- CD34+ HPC displayed commitment potential for both ILC3 and NK cells and the differentiation fate towards these two cell lineages was determined by cytokine and aryl hydrocarbon receptor (AhR) signaling. Thus, we propose that RORM-NM-3t+ CD34+ cells represent human lineage-specified progenitors of IL-22+ ILC3 and that tonsils as well as intestinal LP might be preferential sites of their differentiation. ILC3, NK cells and the CD34+ HPC subsets were sorted from tonsils of 6 distinct donors to purity above 95%. cRNA of the sorted cell populations was hybridized to an Agilent Whole Human Genome Oligo Microarrays (8x60K v2, Design ID 039494)
2014-11-25 | E-GEOD-63197 | biostudies-arrayexpress
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
Project description:Understanding how cellular function is imprinted during development requires the identification of factors controlling lineage specification and commitment, and the intermediate progenitors in which they act. Using population level and single cell approaches, we examine transcriptional and functional heterogeneity within early innate lymphoid cells (ILC) progenitors. We identify a developmental bifurcation toward dendritic cell fate that reveals the uncommitted state of early specified ILC progenitors. We subsequently characterize an ILC-commitment checkpoint controlled by the transcription factor TCF-1. The present study reveals unexpected heterogeneity within early innate progenitor populations, and characterizes lineage infidelity that accompanies early ILC specification prior to commitment.
2019-04-22 | GSE113766 | GEO
Project description:Understanding how cellular function is imprinted during development requires the identification of factors controlling lineage specification and commitment, and the intermediate progenitors in which they act. Using population level and single cell approaches, we examine transcriptional and functional heterogeneity within early innate lymphoid cells (ILC) progenitors. We identify a developmental bifurcation toward dendritic cell fate that reveals the uncommitted state of early specified ILC progenitors. We subsequently characterize an ILC-commitment checkpoint controlled by the transcription factor TCF-1. The present study reveals unexpected heterogeneity within early innate progenitor populations, and characterizes lineage infidelity that accompanies early ILC specification prior to commitment.
2019-04-22 | GSE113765 | GEO
Project description:A key feature of immune tolerance is the ability to distinguish pathogens from innocuous signals including dietary antigens, but the precise mechanisms of oral tolerance induction and the key cellular actors have remained unclear. Classical dendritic cells (cDCs) have previously been implicated in the generation of regulatory T cells (Tregs) and T-cell anergy in response to food antigens in gut-associated lymphoid tissue1, but here we demonstrate that RORγt-lineage antigen-presenting cells (APCs), specifically RORγt-lineage cells expressing the Autoimmune Regulator (Aire) gene – referred to as RORγt eTACs – are the critical APC population required for oral tolerance induction. We reconcile the identity of these rare RORγt-lineage APC populations across new and all known single-cell transcriptomic datasets to establish consensus identities and show that RORγt eTACs2 are a unique myeloid-derived lineage distinct from innate lymphoid cells (ILCs) which are both necessary and sufficient for oral tolerance induction.
2025-04-15 | GSE273746 | GEO
Project description:Innate lymphoid cells (ILCs) were generated in vitro from CD34+ hematopoietic progenitors derived from umbilical cord blood, and RNA sequencing was performed on the ILC subsets generated to assess global phenotype and compare lineage signatures with each other and to those from ex vivo isolated ILCs.
2021-08-25 | GSE141504 | GEO
Project description:The immune system must distinguish pathogens from innocuous dietary antigens, but the precise mechanisms and cellular actors involved are unclear. Here, we demonstrate that RORγt-lineage antigen-presenting cells (APCs) expressing the Autoimmune Regulator (Aire) gene – referred to as RORγt eTACs – are required for oral tolerance. Using lineage tracing and single-cell sequencing, we show that RORγt eTACs are of a myeloid-derived lineage and establish consensus identities for all RORγt-lineage APCs. We found that RORγt eTACs, but not type 3 innate lymphoid cells, are necessary and sufficient for oral tolerance induction. Upon depletion of RORγt eTACs, mice fail to develop food-specific Tregs and display severe delayed-type hypersensitivity responses. These findings establish RORγt eTACs as critical mediators of oral tolerance and suggest novel targets to modulate immune tolerance.
2025-04-15 | GSE291696 | GEO
Project description:The immune system must distinguish pathogens from innocuous dietary antigens, but the precise mechanisms and cellular actors involved are unclear. Here, we demonstrate that RORγt-lineage antigen-presenting cells (APCs) expressing the Autoimmune Regulator (Aire) gene – referred to as RORγt eTACs – are required for oral tolerance. Using lineage tracing and single-cell sequencing, we show that RORγt eTACs are of a myeloid-derived lineage and establish consensus identities for all RORγt-lineage APCs. We found that RORγt eTACs, but not type 3 innate lymphoid cells, are necessary and sufficient for oral tolerance induction. Upon depletion of RORγt eTACs, mice fail to develop food-specific Tregs and display severe delayed-type hypersensitivity responses. These findings establish RORγt eTACs as critical mediators of oral tolerance and suggest novel targets to modulate immune tolerance.
2025-04-15 | GSE291411 | GEO
Project description:The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision. The validity of this model has recently been questioned in the mouse, however little is known concerning lineage potential of human progenitors. Here we provide a comprehensive analysis of the human hematopoietic hierarchy by clonally mapping the developmental potential of 7 progenitor classes from neonatal cord blood and adult bone marrow. Human multi-lymphoid progenitors, identified as a distinct population of Thy1-/loCD45RA+ cells within the CD34+CD38- stem cell compartment, gave rise to all lymphoid cell types, as well as monocytes, macrophages, and dendritic cells, indicating that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation. Total RNA was extracted from 5 - 10,000 sorted cord blood progenitor cells to compare gene expression
2010-06-23 | E-GEOD-21973 | biostudies-arrayexpress