Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans

The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXL+ SIGLEC6+ pre-DC, DC2 and DC3. The origin of this heterogeneity is unknown. Using highdimensional analysis, in vitro differentiation, and an allelic series of human IRF8 deficiency, we demonstrated that cDC2 (CD1c+ DC) heterogeneity originates from two distinct pathways of development. The lymphoidprimed IRF8hi pathway, marked by CD123 and BTLA, carried pDC, cDC1, and DC2 trajectories, while the common myeloid IRF8lo pathway, expressing SIRPA, formed DC3s and monocytes. We traced distinct trajectories through the granulocyte-macrophage progenitor (GMP) compartment showing that AXL+ SIGLEC6+ pre-DCs mapped exclusively to the DC2 pathway. In keeping with their lower requirement for IRF8, DC3s expand to replace DC2s in human partial IRF8 deficiency

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Author Correction: Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi

Correction to: Nature Communications, published online 19 July 2023 In the original version of this article, the given and family names of Armando Del Rio Hernandez were incorrectly structured. The name was displayed correctly in all versions at the time of publication. In this article the affiliation details for Nordine Helassa were incorrectly given as ‘7. Centre for Cardiovascular Science, Department of Cardiovascular Science and Metabolic Medicine, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.’ but should have been ‘7. Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.’. The original article has been corrected