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Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations.

ABSTRACT: Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations.

PROVIDER: PRJNA934285 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23438400_1.fastq.gz	Fastqsanger.gz
	SRR23438400_2.fastq.gz	Fastqsanger.gz
	SRR23438401_1.fastq.gz	Fastqsanger.gz
	SRR23438401_2.fastq.gz	Fastqsanger.gz
	SRR23438402_1.fastq.gz	Fastqsanger.gz

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Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations [scRNA-seq]

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Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations [scRNA-seq]

Project description:Innate lymphoid cells (ILCs) are highly plastic immune cells that have been separated into 3 main subsets, characterized by distinct phenotypic and functional profiles. Using single cell approaches, heightened heterogeneity of mouse ILCs has been recently appreciated, imprinted by tissue signals that shape their transcriptome and epigenome. Intra-subset diversity has also been observed in human ILCs. However, combined transcriptomic and epigenetic analyses of single ILCs in humans are lacking. Here we show high transcriptional and epigenetic heterogeneity among human circulating ILCs in healthy individuals. We describe phenotypically distinct subclusters within main circulating ILC populations. We show diverse chromatin accessibility within main ILC subsets, compatible with differentially poised states. We validate the use of this healthy donor-based analysis as resource dataset to infer ILC changes occurring in disease conditions. Overall, our work provides new insights in the complex human ILC biology. We anticipate our work to be a starting point to facilitate hypothesis-driven studies in patients, without the need to perform single cell OMICs using precious patients’ material

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Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations.

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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.

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Systemic human ILC precursors provide a substrate for tissue ILC differentiation

Project description:Innate lymphoid cells (ILC) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We observed that a population of CD117+ ILC from peripheral blood (PB) of healthy donors does not represent any conical ILC subset, but expressed marker (CD117) commonly expressed by hemato-lymphoid progenitors. We therefore hypothesized PB CD117+ ILC might include uncommitted lymphoid precursors. In order to further understand the identity of PB CD117+ ILC, we profiled the transcriptome of highly purified circulating CD117+ ILC compared to CD34+ HSC, the latter representing immature hematopoietic progenitors with multi-lineage potential. Clear differences in gene expression profiles emerged, with a large cluster of 1540 genes expressed at substantially higher levels in CD117+ ILC. In contrast, CD34+ HSC cells highly expressed genes involved in the broad development of diverse hematopoietic lineages. Compared to HSC, CD117+ ILC express high levels of TF that have been shown to be essential for murine ILC development and we did not detect transcripts characteristic of T and B cells development. Transcriptomic analysis suggested that CD117+ ILC represent lymphoid-biased progenitors carrying a TF expression profile resembling a multi-potent ILC precursor (ILCP).

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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.

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