Ly6DSiglec-H Precursors Contribute to Conventional Dendritic Cells Via a Zbtb46Ly6D Intermediary Stage

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jun 15

PMID 35705536

Authors

Konstantin Lutz

Andrea Musumeci

Christopher Sie

Ezgi Dursun

Elena Winheim

Johannes Bagnoli

Christoph Ziegenhain

Lisa Rausch

Volker Bergen

Malte D Luecken

Robert A J Oostendorp

Barbara U Schraml

Fabian J Theis

Wolfgang Enard

Thomas Korn

Anne B Krug

Affiliations

Soon will be listed here.

Abstract

Plasmacytoid and conventional dendritic cells (pDC and cDC) are generated from progenitor cells in the bone marrow and commitment to pDCs or cDC subtypes may occur in earlier and later progenitor stages. Cells within the CD11cMHCIISiglec-HCCR9 DC precursor fraction of the mouse bone marrow generate both pDCs and cDCs. Here we investigate the heterogeneity and commitment of subsets in this compartment by single-cell transcriptomics and high-dimensional flow cytometry combined with cell fate analysis: Within the CD11cMHCIISiglec-HCCR9 DC precursor pool cells expressing high levels of Ly6D and lacking expression of transcription factor Zbtb46 contain CCR9B220 immediate pDC precursors and CCR9B220 (lo-lo) cells which still generate pDCs and cDCs in vitro and in vivo under steady state conditions. cDC-primed cells within the Ly6DZbtb46 lo-lo precursors rapidly upregulate Zbtb46 and pass through a Zbtb46Ly6D intermediate stage before acquiring cDC phenotype after cell division. Type I IFN stimulation limits cDC and promotes pDC output from this precursor fraction by arresting cDC-primed cells in the Zbtb46Ly6D stage preventing their expansion and differentiation into cDCs. Modulation of pDC versus cDC output from precursors by external factors may allow for adaptation of DC subset composition at later differentiation stages.

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