Mapping the human DC lineage through the integration of high-dimensional techniques

See, Peter; Dutertre, Charles–Antoine; Chen, Jinmiao; Günther, Patrick; McGovern, Naomi; Irac, Sergio Erdal; Gunawan, Merry; Beyer, Marc; Händler, Kristian; Duan, Kaibo; Sumatoh, Hermi; Ruffin, Nicolas; Jouve, Mabel; Gea‐Mallorquí, Ester; Hennekam, Raoul C. M.; Lim, Tony Kiat Hon; Yip, Chan Chung; Wen, Ming; Malleret, Benoît; Low, Ivy; Shadan, Nurhidaya Binte; Fen, Charlene Foong Shu; Tay, Alicia; Lum, Josephine; Zolezzi, Francesca; Larbi, Anis; Poidinger, Michael; Chan, Jerry Kok Yen; Chen, Yi‐Ping Phoebe; Rénia, Laurent; Haniffa, Muzlifah; Benaroch, Philippe; Schlitzer, Andreas; Schultze, Joachim L.; Newell, Evan W.; Ginhoux, Florent

doi:10.1126/science.aag3009

Cited by 475 publications

(612 citation statements)

References 76 publications

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“…(For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.) population of pre-cDCs expressing AXL that highly expresses co-stimulatory molecules (See et al, 2017;Villani et al, 2017). Although it can be deduced from these studies that bona fide pDCs still outnumber contaminating cDCs using this gating strategy, it is not known whether the extent of pre-cDC contamination varies between males and females or whether it is affected by infection.…”

Section: Discussionmentioning

confidence: 68%

TLR7 polymorphism, sex and chronic HBV infection influence plasmacytoid DC maturation by TLR7 ligands

et al. 2018

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A B S T R A C TTLR7 agonists are of high interest for the treatment of cancer, auto-immunity and chronic viral infections. They are known to activate plasmacytoid dendritic cells (pDCs) to produce high amounts of Type I Interferon (IFN) and to facilitate T and B cell responses, the latter with the help of maturation markers such as CD40, CD80 and CD86. The TLR7 single nucleotide polymorphism (SNP) rs179008 (GLn11Leu), sex and chronic viral infection have all been reported to influence pDC IFN production. It is unknown, however, whether these factors also influence pDC phenotypic maturation and thereby IFN-independent pDC functions. Furthermore, it is unclear whether SNP rs179008 influences HBV susceptibility and/or clearance.Here we investigated whether the SNP rs179008, sex and HBV infection affected phenotypic maturation of pDCs from 38 healthy individuals and 28 chronic HBV patients. In addition, we assessed SNP prevalence in a large cohort of healthy individuals (n = 231) and chronic HBV patients (n = 1054).Consistent with previous reports, the rs179008 variant allele was largely absent in Asians and more prevalent in Caucasians. Among Caucasians, the SNP was equally prevalent in healthy and chronically infected males. The SNP was, however, significantly more prevalent in healthy females than in those with chronic HBV infection (42 versus 28%), suggesting that in females it may offer protection from chronic infection. Ex vivo experiments demonstrated that induction of the co-stimulatory molecules CD40 and CD86 by TLR7 ligands, but not TLR9 ligands, was augmented in pDCs from healthy SNP-carrying females. Furthermore, CD80 and CD86 upregulation was more pronounced in females independent of the SNP. Lastly, our data suggested that chronic HBV infection impairs pDC maturation. These findings provide insight into factors determining TLR7 responses, which is important for further clinical development of TLR7-based therapies.

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Section: Discussionmentioning

confidence: 68%

TLR7 polymorphism, sex and chronic HBV infection influence plasmacytoid DC maturation by TLR7 ligands

et al. 2018

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“…Our study identified a progenitor marked as CD34 -CD123 + cells in cord blood and in human dermis that gave rise primarily to the CD11c + CD1c + CD5 + DCs, which we referred to as "pre-CD5 + DCs." Pre-cDCs were initially found in humans within the CD34 -CD123 -fractions (28); however, a recent study reported the presence of CD123 hi CD33 + CD45RA + CD303 + pre-DCs in peripheral blood (47). In contrast with See et al, our gating strategy excluded all the cells that expressed the pDC marker CD303 / BDCA-2; thus, perhaps we looked at a distinct, possibly more committed, pre-cDC subset.…”

Section: Cd1cmentioning

confidence: 78%

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

Korenfeld¹,

Gorvel²,

Munk³

et al. 2017

JCI Insight

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“…This is in line with previous studies suggesting mixed myeloid and lymphoid origin of pDCs 29,[37][38][39][40] and could help to resolve this controversy. Hence, our study sheds light on the origin of pDCs in the bone marrow, adding another piece to the puzzle of pDC versus cDC differentiation, which is still subject of intense research 37,38,[41][42][43] . As another example, we note that FateID recovered a recently characterized bipotent progenitor of monocytes and neutrophils 3 ( Supplementary Fig.…”

Section: Cc-by-nc-nd 40 International License Not Peer-reviewed) Ismentioning

confidence: 86%

FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data

Herman

Sagar

Grün

2017

Preprint

159

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Differentiation of multipotent cells is a complex process governed by interactions of thousands of genes subject to substantial expression fluctuations. Resolving cell state heterogeneity arising during this process requires quantification of gene expression within individual cells. However, computational methods linking this heterogeneity to biases towards distinct cell fates are not well established. Here, we perform deep single-cell transcriptome sequencing of ~2,000 bone-marrow derived mouse hematopoietic progenitors enriched for lymphoid lineages. To resolve subtle transcriptome priming indicative of distinct lineage biases, we developed FateID, an iterative supervised learning algorithm for the probabilistic quantification of cell fate bias. FateID delineates domains of fate bias within progenitor populations and permits the derivation of high-resolution differentiation trajectories, revealing a common progenitor population of B cells and plasmacytoid dendritic cells, which we validated by in vitro differentiation assays. We expect that FateID will enhance our understanding of the process of cell fate choice in complex multi-lineage differentiation systems. INTRODUCTIONRecent studies utilizing scRNA-seq 1-5 and single-cell lineage tracing techniques 6-8 , call into question the traditional view of hematopoietic differentiation as a sequence of binary fate choices giving rise to a succession of increasingly fate restricted progenitor types 9 . Evidence from these studies rather suggests early cell fate priming starting at the level of multipotent progenitors (MPP) or even within the HSC pool. Pronounced heterogeneity of common myeloid progenitors (CMP) was elucidated with high resolution 1 , and an early fate bias emerging in human short term HSCs was suggested in a more recent study 2 . However, heterogeneity of lymphoid progenitors has not been well investigated with single-cell resolution. Since lymphoid progenitor heterogeneity was previously found by flow cytometry 10,11 , utilizing distinct sets of cell surface markers in combination with differentiation assays, we here perform an scRNA-seq analysis to comprehensively elucidate heterogeneity across lymphoid progenitors purified from the bone-marrow of adult mice. Although a number of methods for lineage reconstruction have been developed [12][13][14][15] , these algorithms are not specifically designed to uncover subtle transcriptome changes and uniquely assign cells to individual branches without accounting for multi-lineage bias. Weak transcriptome modulations also remain undiscovered by state-of-the-art clustering methods, which partition cells into groups without accounting for the co-existence of fate bias towards multiple lineages within individual cells. To elucidate the process of cell fate emergence, we introduce FateID, a computational method for the quantification of fate bias, manifested by subtle lineage specific transcriptome modulations within a multipotent progenitor . CC-BY-NC-ND 4.0 International license not peer-reviewed) is the aut...

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Mapping the human DC lineage through the integration of high-dimensional techniques

Cited by 475 publications

References 76 publications

TLR7 polymorphism, sex and chronic HBV infection influence plasmacytoid DC maturation by TLR7 ligands

TLR7 polymorphism, sex and chronic HBV infection influence plasmacytoid DC maturation by TLR7 ligands

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data

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