Journal Article

DZNE-2026-00308

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A single-cell transcriptional reference for the functional and developmental diversity of neonatal innate lymphoid cells.

Bennstein, S. B. ; Reiß, J. ; Raba, K. ; Pham, T. X. U. ; Paulusch, S.DZNE* ; De Domenico, E.DZNE* ; Niehues, T. ; Fischer, J. C. ; Kögler, G. ; Beyer, M. D.DZNE* ; Uhrberg, M.

2026
Cell Press Maryland Heights, MO

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Please use a persistent id in citations: doi:10.1016/j.celrep.2026.117000

Abstract: Circulating innate lymphoid cells (cILCs) comprise a complex mixture of subsets with effector functions and progenitor potential toward mature ILCs and natural killer (NK) cells. Here, we dissected cord blood (CB) cILC complexity using single-cell RNA sequencing (RNA-seq) combined with developmental and functional analyses. cILC1s comprise six different subsets, with four showing different maturation degrees and two resembling NK cell progenitors. Despite previously described transcriptional similarity to T cells, the developmental potential of cILC1s was restricted to NK cells using an artificial thymic organoid (ATO) model. cILC2s could be divided into four main subsets: CD161+, CD117+, activated cILC2s, and cytotoxic cILC2s. Finally, a CD161+CD28+CD117low ILC3 subset was identified that secreted IFNγ upon co-stimulation with a CD28 superagonist, suggesting an alternative activation stimulus for cILC3s. Altogether, this in-depth analysis provides a detailed picture of cILC diversity in immunologically naive CB and constitutes a versatile resource for further exploration of their translational potential.

Keyword(s): Humans (MeSH) ; Immunity, Innate (MeSH) ; Single-Cell Analysis: methods (MeSH) ; Lymphocytes: metabolism (MeSH) ; Lymphocytes: cytology (MeSH) ; Lymphocytes: immunology (MeSH) ; Killer Cells, Natural: immunology (MeSH) ; Killer Cells, Natural: cytology (MeSH) ; Killer Cells, Natural: metabolism (MeSH) ; Fetal Blood: cytology (MeSH) ; Transcription, Genetic (MeSH) ; Cell Differentiation (MeSH) ; Infant, Newborn (MeSH) ; CP: developmental biology ; CP: immunology ; ILCs ; NK cells ; human ; innate lymphoid cells ; natural killer cells ; scRNA-seq ; umbilical cord blood

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Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
2. Immunogenomics and Neurodegeneration (AG Beyer)
3. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 351 - Brain Function (POF4-351) (POF4-351)
3. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2026

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