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Single‐cell transcriptome analysis reveals the dynamics of human immune cells during early fetal skin development

Xu, Yingping, Zhang, Jun, Hu, Yongfei, Li, Xuefei, Sun, Lihua, Peng, Yu, Sun, Yuzhe, Liu, Bing, Bian, Zhilei, Rong, Zhili·2021·Cell Reports

Abstract

The immune system of skin develops in stages in mice. However, the developmental dynamics of immune cells in human skin remains elusive. Here, we perform transcriptome profiling of CD45 + hematopoietic cells in human fetal skin at an estimated gestational age of 10-17 weeks by single-cell RNA sequencing. A total of 13 immune cell types are identified. Skin macrophages show dynamic heterogeneity over the course of skin development. A major shift in lymphoid cell developmental states occurs from the first to the second trimester that implies an in situ differentiation process. Gene expression analysis reveals a typical developmental program in immune cells in accordance with their functional maturation, possibly involving metabolic reprogramming. Finally, we identify transcription factors (TFs) that potentially regulate cellular transitions by comparing TFs and TF target gene networks. These findings provide detailed insight into how the immune system of the human skin is established during development.

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Research works printed but not linked: 94

  1. Ander, 2019, Immune responses at the maternal-fetal interface, Sci. Immunol., 4, eaat6114, 10.1126/sciimmunol.aat6114 · DOI
  2. Angelin, 2017, Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments, Cell Metab., 25, 1282, 10.1016/j.cmet.2016.12.018 · DOI
  3. Asare, 2017, Coupling organelle inheritance with mitosis to balance growth and differentiation, Science, 355, eaah4701, 10.1126/science.aah4701 · DOI
  4. Barbie, 2009, Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1, Nature, 462, 108, 10.1038/nature08460 · DOI
  5. Becht, 2018, Dimensionality reduction for visualizing single-cell data using UMAP, Nat. Biotechnol., 372, 38
  6. Bian, 2020, Deciphering human macrophage development at single-cell resolution, Nature, 582, 571, 10.1038/s41586-020-2316-7 · DOI
  7. Chapman, 2020, Metabolic coordination of T cell quiescence and activation, Nat. Rev. Immunol., 20, 55, 10.1038/s41577-019-0203-y · DOI
  8. Chen, 2018, CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway, Immunity, 49, 464, 10.1016/j.immuni.2018.08.010 · DOI
  9. Colonna, 2018, Innate Lymphoid Cells: Diversity, Plasticity, and Unique Functions in Immunity, Immunity, 48, 1104, 10.1016/j.immuni.2018.05.013 · DOI
  10. Constantinides, 2015, PLZF expression maps the early stages of ILC1 lineage development, Proc. Natl. Acad. Sci. USA, 112, 5123, 10.1073/pnas.1423244112 · DOI
  11. Cooper, 2009, Hidden talents of natural killers: NK cells in innate and adaptive immunity, EMBO Rep., 10, 1103, 10.1038/embor.2009.203 · DOI
  12. Crinier, 2018, High-Dimensional Single-Cell Analysis Identifies Organ-Specific Signatures and Conserved NK Cell Subsets in Humans and Mice, Immunity, 49, 971, 10.1016/j.immuni.2018.09.009 · DOI · Paper page
  13. Darrasse-Jèze, 2005, Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses, Blood, 105, 4715, 10.1182/blood-2004-10-4051 · DOI
  14. Dhariwala, 2020, Developing Human Skin Contains Lymphocytes Demonstrating a Memory Signature, Cell Rep Med, 1, 100132, 10.1016/j.xcrm.2020.100132 · DOI
  15. Di Nuzzo, 2009, Densities, distribution and phenotypic expression of T cells in human fetal skin, Arch. Dermatol. Res., 301, 753, 10.1007/s00403-009-0943-9 · DOI
  16. Dutt, 2007, Naive and memory T cells induce different types of graft-versus-host disease, J. Immunol., 179, 6547, 10.4049/jimmunol.179.10.6547 · DOI
  17. Floriddia, 2020, Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury, Nat. Commun., 11, 5860, 10.1038/s41467-020-19453-x · DOI
  18. Freud, 2017, The Broad Spectrum of Human Natural Killer Cell Diversity, Immunity, 47, 820, 10.1016/j.immuni.2017.10.008 · DOI
  19. Gentek, 2018, Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells, Immunity, 48, 1160, 10.1016/j.immuni.2018.04.025 · DOI · Paper page
  20. Gentek, 2018, Epidermal γδ T cells originate from yolk sac hematopoiesis and clonally self-renew in the adult, J. Exp. Med., 215, 2994, 10.1084/jem.20181206 · DOI
  21. Ginhoux, 2016, Tissue-Resident Macrophage Ontogeny and Homeostasis, Immunity, 44, 439, 10.1016/j.immuni.2016.02.024 · DOI · Paper page
  22. Griebel, 2014, NOD-like receptor cooperativity in effector-triggered immunity, Trends Immunol., 35, 562, 10.1016/j.it.2014.09.005 · DOI
  23. Harshuk-Shabso, 2020, Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock, Nat. Commun., 11, 5114, 10.1038/s41467-020-18643-x · DOI
  24. Haynes, 1988, Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues, J. Exp. Med., 168, 1061, 10.1084/jem.168.3.1061 · DOI
  25. He, 2016, Prokineticin 2 Plays a Pivotal Role in Psoriasis, EBioMedicine, 13, 248, 10.1016/j.ebiom.2016.10.022 · DOI
  26. Holt, 2000, The development of the immune system during pregnancy and early life, Allergy, 55, 688, 10.1034/j.1398-9995.2000.00118.x · DOI
  27. Hoyler, 2012, The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells, Immunity, 37, 634, 10.1016/j.immuni.2012.06.020 · DOI
  28. Hu, 2018, Embryonic skin development and repair, Organogenesis, 14, 46, 10.1080/15476278.2017.1421882 · DOI
  29. Hutter, 2013, The Role of PPARs in Placental Immunology: A Systematic Review of the Literature, PPAR Res., 2013, 970276, 10.1155/2013/970276 · DOI
  30. Kaplan, 2017, Ontogeny and function of murine epidermal Langerhans cells, Nat. Immunol., 18, 1068, 10.1038/ni.3815 · DOI
  31. Kiselev, 2018, scmap: projection of single-cell RNA-seq data across data sets, Nat. Methods, 15, 359, 10.1038/nmeth.4644 · DOI
  32. Koo, 2018, Interplay between YAP/TAZ and Metabolism, Cell Metab., 28, 196, 10.1016/j.cmet.2018.07.010 · DOI
  33. Korsunsky, 2019, Fast, sensitive and accurate integration of single-cell data with Harmony, Nat. Methods, 16, 1289, 10.1038/s41592-019-0619-0 · DOI · Paper page
  34. Krabbendam, 2018, New insights into the function, development, and plasticity of type 2 innate lymphoid cells, Immunol. Rev., 286, 74, 10.1111/imr.12708 · DOI
  35. Kupari, 2021, Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain, Nat. Commun., 12, 1510, 10.1038/s41467-021-21725-z · DOI
  36. Lian, 2018, Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation, eLife, 7, e36158, 10.7554/eLife.36158 · DOI
  37. Liang, 2012, HOXA5 inhibits keratinocytes growth and epidermal formation in organotypic cultures in vitro and in vivo, J. Dermatol. Sci., 66, 197, 10.1016/j.jdermsci.2012.02.019 · DOI
  38. Lim, 2017, Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation, Cell, 168, 1086, 10.1016/j.cell.2017.02.021 · DOI
  39. Liu, 2019, Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells, Cell, 178, 1509, 10.1016/j.cell.2019.08.009 · DOI · Paper page
  40. Loftus, 2018, Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice, Nat. Commun., 9, 2341, 10.1038/s41467-018-04719-2 · DOI
  41. Ludtmann, 2014, Nrf2 affects the efficiency of mitochondrial fatty acid oxidation, Biochem. J., 457, 415, 10.1042/BJ20130863 · DOI
  42. Mace, 2017, Biallelic mutations in IRF8 impair human NK cell maturation and function, J. Clin. Invest., 127, 306, 10.1172/JCI86276 · DOI
  43. Macosko, 2015, Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets, Cell, 161, 1202, 10.1016/j.cell.2015.05.002 · DOI · Paper page
  44. Martínez, 2011, PPARα agonists regulate lipid metabolism and nitric oxide production and prevent placental overgrowth in term placentas from diabetic rats, J. Mol. Endocrinol., 47, 1, 10.1530/JME-10-0173 · DOI
  45. McGovern, 2015, Dendritic cells in humans—from fetus to adult, Int. Immunol., 27, 65, 10.1093/intimm/dxu091 · DOI
  46. McGrath, 2015, Early hematopoiesis and macrophage development, Semin. Immunol., 27, 379, 10.1016/j.smim.2016.03.013 · DOI
  47. Melichar, 2007, Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13, Science, 315, 230, 10.1126/science.1135344 · DOI · Paper page
  48. Méndez-Enríquez, 2019, Mast Cells and Their Progenitors in Allergic Asthma, Front. Immunol., 10, 821, 10.3389/fimmu.2019.00821 · DOI
  49. Michelet, 2018, Metabolic reprogramming of natural killer cells in obesity limits antitumor responses, Nat. Immunol., 19, 1330, 10.1038/s41590-018-0251-7 · DOI
  50. Nyström, 2019, Matrix molecules and skin biology, Semin. Cell Dev. Biol., 89, 136, 10.1016/j.semcdb.2018.07.025 · DOI · Paper page
  51. Ohls, 1995, Neutrophil pool sizes and granulocyte colony-stimulating factor production in human mid-trimester fetuses, Pediatr. Res., 37, 806, 10.1203/00006450-199506000-00022 · DOI
  52. Park, 2018, Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation, Front. Immunol., 9, 1859, 10.3389/fimmu.2018.01859 · DOI
  53. Park, 2020, A cell atlas of human thymic development defines T cell repertoire formation, Science, 367, 367, 10.1126/science.aay3224 · DOI
  54. Plum, 2020, Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation, Immunity, 52, 404, 10.1016/j.immuni.2020.01.012 · DOI
  55. Possot, 2011, Notch signaling is necessary for adult, but not fetal, development of RORγt(+) innate lymphoid cells, Nat. Immunol., 12, 949, 10.1038/ni.2105 · DOI
  56. Qiu, 2017, Reversed graph embedding resolves complex single-cell trajectories, Nat. Methods, 14, 979, 10.1038/nmeth.4402 · DOI · Paper page
  57. Renoux, 2015, Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues, Immunity, 43, 394, 10.1016/j.immuni.2015.07.011 · DOI
  58. Rhodes, 2019, Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection, Front. Immunol., 10, 1088, 10.3389/fimmu.2019.01088 · DOI
  59. Rosmaraki, 2001, Identification of committed NK cell progenitors in adult murine bone marrow, Eur. J. Immunol., 31, 1900, 10.1002/1521-4141(200106)31:6<1900::AID-IMMU1900>3.0.CO;2-M · DOI
  60. Rousselle, 2019, Extracellular matrix contribution to skin wound re-epithelialization, Matrix Biol., 75-76, 12, 10.1016/j.matbio.2018.01.002 · DOI
  61. Saito, 2006, Gene expression profiling of human mast cell subtypes: an in silico study, Allergol. Int., 55, 173, 10.2332/allergolint.55.173 · DOI
  62. Schneider, 2019, Tissue-Resident Group 2 Innate Lymphoid Cells Differentiate by Layered Ontogeny and In Situ Perinatal Priming, Immunity, 50, 1425, 10.1016/j.immuni.2019.04.019 · DOI
  63. Schuster, 2009, HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells, J. Exp. Med., 206, 169, 10.1084/jem.20081747 · DOI
  64. Schuster, 2012, Phenotypic characterization of leukocytes in prenatal human dermis, J. Invest. Dermatol., 132, 2581, 10.1038/jid.2012.187 · DOI
  65. Schuster, 2014, Human embryonic epidermis contains a diverse Langerhans cell precursor pool, Development, 141, 807, 10.1242/dev.102699 · DOI
  66. Scoville, 2016, A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets, Immunity, 44, 1140, 10.1016/j.immuni.2016.04.007 · DOI
  67. See, 2017, Mapping the human DC lineage through the integration of high-dimensional techniques, Science, 356, 356, 10.1126/science.aag3009 · DOI
  68. Sengel, 1985, Role of extracellular matrix in the development of skin and cutaneous appendages, Prog. Clin. Biol. Res., 171, 123
  69. Shannon, 2003, Cytoscape: a software environment for integrated models of biomolecular interaction networks, Genome Res., 13, 2498, 10.1101/gr.1239303 · DOI · Paper page
  70. Shyh-Chang, 2013, Stem cell metabolism in tissue development and aging, Development, 140, 2535, 10.1242/dev.091777 · DOI
  71. Simões, 2020, Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair, Nat. Commun., 11, 600, 10.1038/s41467-019-14263-2 · DOI
  72. Spits, 2013, Innate lymphoid cells--a proposal for uniform nomenclature, Nat. Rev. Immunol., 13, 145, 10.1038/nri3365 · DOI
  73. Stegen, 2020, Glutamine Metabolism Controls Chondrocyte Identity and Function, Dev. Cell, 53, 530, 10.1016/j.devcel.2020.05.001 · DOI
  74. Stelnicki, 1998, HOX homeobox genes exhibit spatial and temporal changes in expression during human skin development, J. Invest. Dermatol., 110, 110, 10.1046/j.1523-1747.1998.00092.x · DOI
  75. Stewart, 2019, Spatiotemporal immune zonation of the human kidney, Science, 365, 1461, 10.1126/science.aat5031 · DOI
  76. Stuart, 2019, Comprehensive Integration of Single-Cell Data, Cell, 177, 1888, 10.1016/j.cell.2019.05.031 · DOI · Paper page
  77. Szklarczyk, 2019, STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets, Nucleic Acids Res., 47, D607, 10.1093/nar/gky1131 · DOI · Paper page
  78. Tallquist, 2017, Redefining the identity of cardiac fibroblasts, Nat. Rev. Cardiol., 14, 484, 10.1038/nrcardio.2017.57 · DOI · Paper page
  79. Taveirne, 2020, The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation, Blood, 136, 288
  80. Tavian, 2005, Embryonic development of the human hematopoietic system, Int. J. Dev. Biol., 49, 243, 10.1387/ijdb.041957mt · DOI · Paper page
  81. Trapnell, 2014, The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells, Nat. Biotechnol., 32, 381, 10.1038/nbt.2859 · DOI · Paper page
  82. Villanova, 2014, Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis, J. Invest. Dermatol., 134, 984, 10.1038/jid.2013.477 · DOI
  83. Wang, 2015, Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities, Stem Cell Res. Ther., 6, 158, 10.1186/s13287-015-0149-3 · DOI
  84. Wang, 2016, NF-E2-related factor 2 deletion facilitates hepatic fatty acids metabolism disorder induced by high-fat diet via regulating related genes in mice, Food Chem. Toxicol., 94, 186, 10.1016/j.fct.2016.06.011 · DOI
  85. Werner, 2020, Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke, Nat. Neurosci., 23, 351, 10.1038/s41593-020-0585-y · DOI · Paper page
  86. Wolf, 2018, SCANPY: large-scale single-cell gene expression data analysis, Genome Biol., 19, 15, 10.1186/s13059-017-1382-0 · DOI · Paper page
  87. Yanez, 2017, The role of macrophages in skin homeostasis, Pflugers Arch., 469, 455, 10.1007/s00424-017-1953-7 · DOI
  88. Yessoufou, 2006, Peroxisome proliferator-activated receptor alpha deficiency increases the risk of maternal abortion and neonatal mortality in murine pregnancy with or without diabetes mellitus: Modulation of T cell differentiation, Endocrinology, 147, 4410, 10.1210/en.2006-0067 · DOI
  89. Yu, 2014, The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor, eLife, 3, e04406, 10.7554/eLife.04406 · DOI
  90. Yudanin, 2019, Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity, Immunity, 50, 505, 10.1016/j.immuni.2019.01.012 · DOI
  91. Zeng, 2019, Single-Cell RNA Sequencing Resolves Spatiotemporal Development of Pre-thymic Lymphoid Progenitors and Thymus Organogenesis in Human Embryos, Immunity, 51, 930, 10.1016/j.immuni.2019.09.008 · DOI
  92. Zhang, 2015, AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors, Nucleic Acids Res., 43, D76, 10.1093/nar/gku887 · DOI
  93. Zhang, 2020, hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets, Genomics Proteomics Bioinformatics, 18, 120, 10.1016/j.gpb.2019.09.006 · DOI
  94. Zhong, 2020, Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells, Immunity, 52, 83, 10.1016/j.immuni.2019.12.001 · DOI

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Metadata

Authors
Xu, Y., Zhang, J., Hu, Y., Li, X., Sun, L., Peng, Y., Sun, Y., Liu, B., Bian, Z., & Rong, Z.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2021-08
Volume
36
Issue
6
Pages
109524
ISSN
2211-1247
Cited by
27
References
12
Language
en

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