Identification of CDC1- and CDC2-committed DC Progenitors Reveals Early Lineage Priming at the Common DC Progenitor Stage in the Bone Marrow

Overview

Journal Nat Immunol

Date 2015 Jun 10

PMID 26054720

Citations 266

Authors

Andreas Schlitzer

V Sivakamasundari

Jinmiao Chen

Hermi Rizal Bin Sumatoh

Jaring Schreuder

Josephine Lum

Benoit Malleret

Sanqian Zhang

Anis Larbi

Francesca Zolezzi

Laurent Renia

Michael Poidinger

Shalin Naik

Evan W Newell

Paul Robson

Florent Ginhoux

Affiliations

Soon will be listed here.

Abstract

Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-H(-)Ly6C(-) pre-DCs) or cDC2 lineage (Siglec-H(-)Ly6C(+) pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.

Citing Articles

Interleukin-12 signaling drives Alzheimer's disease pathology through disrupting neuronal and oligodendrocyte homeostasis.

Schneeberger S, Kim S, Geesdorf M, Friebel E, Eede P, Jendrach M Nat Aging. 2025; .

PMID: 40082619 DOI: 10.1038/s43587-025-00816-2.

Langerhans Cells Drive Tfh and B Cell Responses Independent of Canonical Cytokine Signals.

Bouteau A, Qin Z, Zurawski S, Zurawski G, Igyarto B bioRxiv. 2025; .

PMID: 39868337 PMC: 11760737. DOI: 10.1101/2025.01.10.632426.

Immunological Regulation of Fibrosis During Heart Failure: It Takes Two to Tango.

Kumar V, Bansal S Biomolecules. 2025; 15(1).

PMID: 39858452 PMC: 11763336. DOI: 10.3390/biom15010058.

Type 2 conventional dendritic cell functional heterogeneity: ontogenically committed or environmentally plastic?.

Leon B Trends Immunol. 2025; 46(2):104-120.

PMID: 39843310 PMC: 11835539. DOI: 10.1016/j.it.2024.12.005.

NR2F6 regulates stem cell hematopoiesis and myelopoiesis in mice.

Woelk J, Narasimhan H, Pfeifhofer-Obermair C, Schraml B, Hermann-Kleiter N Front Immunol. 2025; 15():1404805.

PMID: 39840064 PMC: 11747239. DOI: 10.3389/fimmu.2024.1404805.

References

Prendergast A, Essers M . Hematopoietic stem cells, infection, and the niche. Ann N Y Acad Sci. 2014; 1310:51-7. DOI: 10.1111/nyas.12400. View

Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H . Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell. 2008; 132(3):487-98. DOI: 10.1016/j.cell.2007.12.033. View

Satpathy A, Briseno C, Lee J, Ng D, Manieri N, Kc W . Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013; 14(9):937-48. PMC: 3788683. DOI: 10.1038/ni.2679. View

Usoskin D, Furlan A, Islam S, Abdo H, Lonnerberg P, Lou D . Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat Neurosci. 2014; 18(1):145-53. DOI: 10.1038/nn.3881. View

Schlitzer A, McGovern N, Teo P, Zelante T, Atarashi K, Low D . IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity. 2013; 38(5):970-83. PMC: 3666057. DOI: 10.1016/j.immuni.2013.04.011. View

Merad M, Sathe P, Helft J, Miller J, Mortha A . The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013; 31:563-604. PMC: 3853342. DOI: 10.1146/annurev-immunol-020711-074950. View

Besson A, Dowdy S, Roberts J . CDK inhibitors: cell cycle regulators and beyond. Dev Cell. 2008; 14(2):159-69. DOI: 10.1016/j.devcel.2008.01.013. View

Wu L, DAmico A, Winkel K, Suter M, Lo D, Shortman K . RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity. 1999; 9(6):839-47. DOI: 10.1016/s1074-7613(00)80649-4. View

Baldridge M, King K, Boles N, Weksberg D, Goodell M . Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. 2010; 465(7299):793-7. PMC: 2935898. DOI: 10.1038/nature09135. View

10.

Essers M, Offner S, Blanco-Bose W, Waibler Z, Kalinke U, Duchosal M . IFNalpha activates dormant haematopoietic stem cells in vivo. Nature. 2009; 458(7240):904-8. DOI: 10.1038/nature07815. View

11.

Mortazavi A, Williams B, McCue K, Schaeffer L, Wold B . Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008; 5(7):621-8. DOI: 10.1038/nmeth.1226. View

12.

Pollen A, Nowakowski T, Shuga J, Wang X, Leyrat A, Lui J . Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat Biotechnol. 2014; 32(10):1053-8. PMC: 4191988. DOI: 10.1038/nbt.2967. View

13.

Tenenbaum J, De Silva V, Langford J . A global geometric framework for nonlinear dimensionality reduction. Science. 2000; 290(5500):2319-23. DOI: 10.1126/science.290.5500.2319. View

14.

Shalek A, Satija R, Shuga J, Trombetta J, Gennert D, Lu D . Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature. 2014; 510(7505):363-9. PMC: 4193940. DOI: 10.1038/nature13437. View

15.

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

16.

Kabashima K, Banks T, Ansel K, Lu T, Ware C, Cyster J . Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity. 2005; 22(4):439-50. DOI: 10.1016/j.immuni.2005.02.007. View

17.

Karsunky H, Merad M, Cozzio A, Weissman I, Manz M . Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J Exp Med. 2003; 198(2):305-13. PMC: 2194067. DOI: 10.1084/jem.20030323. View

18.

Miller J, Brown B, Shay T, Gautier E, Jojic V, Cohain A . Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol. 2012; 13(9):888-99. PMC: 3985403. DOI: 10.1038/ni.2370. View

19.

Persson E, Uronen-Hansson H, Semmrich M, Rivollier A, Hagerbrand K, Marsal J . IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation. Immunity. 2013; 38(5):958-69. DOI: 10.1016/j.immuni.2013.03.009. View

20.

Gautier E, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S . Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol. 2012; 13(11):1118-28. PMC: 3558276. DOI: 10.1038/ni.2419. View