Deciphering human macrophage development at single-cell resolution

Bian, Zhilei; Gong, Yandong; Huang, Tao; Lee, Christopher Zhe Wei; Bian, Lihong; Bai, Zhijie; Shi, Hui; Zeng, Yang; Liu, Chen; He, Jian; Zhou, Jie; Li, Xianlong; Li, Zongcheng; Ni, Yanli; Ma, Chunyu; Cui, Lei; Zhang, Rui; Chan, Jerry Kok Yen; Ng, Lai Guan; Lan, Yu; Ginhoux, Florent; Liu, Bing

doi:10.1038/s41586-020-2316-7

Cited by 352 publications

(343 citation statements)

References 47 publications

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“…HBCs are predicted to be primitive macrophages derived directly from progenitors independent of monocytes. A recent study characterizing the transcriptional landscape of human macrophage development identified a population of true primitive YS macrophages (YS_Mac1) from a Carnegie stage 11 embryo (∼4 wk after conception; Bian et al, 2020 ). Consistent with their predicted primitive origins, HBCs are enriched for a gene signature derived from YS_Mac1, but not embryonic monocytes ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2 A and Data S1 ). Integration of first-trimester placental ( Vento-Tormo et al, 2018 ) and early human fetal myeloid scRNA-seq ( Bian et al, 2020 ) datasets reveals a high degree of transcriptional similarity between HBCs and primitive YS_Mac1 ( Fig. 2, B and C ).…”

Section: Resultsmentioning

confidence: 99%

“… First-trimester HBCs are transcriptionally similar to primitive macrophages and proliferate in situ. (A) Heatmap of placental scRNA-seq cluster mean enrichment scores for extraembryonic YS macrophage and embryonic monocyte gene signatures ( Bian et al, 2020 ). Endo, endothelial cells; EVT, extravillous trophoblast; Fibro, fibroblasts; VCT, villous cytotrophoblast; VCTp, proliferating villous cytotrophoblast.…”

Section: Resultsmentioning

confidence: 99%

“…Endo, endothelial cells; EVT, extravillous trophoblast; Fibro, fibroblasts; VCT, villous cytotrophoblast; VCTp, proliferating villous cytotrophoblast. (B) UMAP visualization of 3,846 single-cell transcriptomes from first-trimester placenta and embryonic myeloid cells ( Bian et al, 2020 ). GMP, granulocyte–monocyte progenitors; pHBC, proliferating HBCs; YS_Mac, YS macrophage; YSMP, YS-derived myeloid-biased progenitors.…”

Section: Resultsmentioning

confidence: 99%

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Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

Thomas

Appios

Zhao

et al. 2020

Journal of Experimental Medicine

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Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR−FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

Thomas

Appios

Zhao

et al. 2020

Journal of Experimental Medicine

Self Cite

124

166

View full text Add to dashboard Cite

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“…The polarization of macrophages confers a heterogeneous function and plasticity depending on the duration of stimulation and microenvironment, which are discrete phenotypes associated with different in ammatory responses, typically termed the M1φ /pro-in ammatory and M2φ /anti-in ammatory macrophages (Gomez Perdiguero et al, 2015;Wynn et al, 2013). The distinction is known to be oversimpli ed, with macrophage dynamic activities spread along the M1-M2 phenotypic spectrum (Bian, 2020;Shapouri-Moghaddam et al, 2018). However, in general, M1φ destroys pathogens by producing a large number of pro-in ammatory cytokines such as IL-1β, TNFα, IL-6 and IL18.…”

Section: Introductionmentioning

confidence: 99%

Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

Duan

Guo

Yang

et al. 2020

Preprint

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Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.

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The Biological Role of Macrophage in Lung and Its Implications in Lung Cancer Immunotherapy

Wang,

Gao,

et al. 2024

Advanced Biology

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The lungs are the largest surface of the body and the most important organ in the respiratory system, which are constantly exposed to the external environment. Tissue Resident Macrophages in lung constitutes the important defense against external pathogens. Macrophages connects the innate and adaptive immune system, and also plays important roles in carcinogenesis and cancer immunotherapy. Lung cancer is the leading cause of cancer‐related death worldwide, with an overall five‐year survival rate of only 21%. Macrophages that infiltrate or aggregate in lung tumor microenvironment are defined as tumor‐associated macrophages (TAMs). TAMs are the main components of immune cells in the lung tumor microenvironment. The differentiation and maturation process of TAMs can be roughly divided into two different types: classical activation pathway produces M1 tumor‐associated macrophages, and bypass activation pathway produces M2 tumor‐associated macrophages. Studies have found that TAMs are related to tumor invasion, metastasis, and treatment resistance, and show potential as a new target for tumor immunotherapy. Therefore, the biological function of macrophages in lung and the role of TAMs in the occurrence, development, and treatment of lung cancer are discussed in this paper.

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Deciphering human macrophage development at single-cell resolution

Cited by 352 publications

References 47 publications

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

The Biological Role of Macrophage in Lung and Its Implications in Lung Cancer Immunotherapy

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