title: Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages.
abstract: Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Using in vivo lineage tracing, we identify a first wave of yolk sac (YS)-derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis. YS progenitors migrate to the embryo proper, including the prospective skin, where they give rise to LC precursors, and the brain rudiment, where they give rise to microglial cells. However, in contrast to microglia, which remain of YS origin throughout life, YS-derived LC precursors are largely replaced by fetal liver monocytes during late embryogenesis. Consequently, adult LCs derive predominantly from fetal liver monocyte-derived cells with a minor contribution of YS-derived cells. Altogether, we establish that adult LCs have a dual origin, bridging early embryonic and late fetal myeloid development.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Immunos Building #3-4, BIOPOLIS, 138648, Singapore.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoeffel
authors.forename: Yilin
authors.initials: Y
authors.lastname: Wang
authors.forename: Melanie
authors.initials: M
authors.lastname: Greter
authors.forename: Peter
authors.initials: P
authors.lastname: See
authors.forename: Pearline
authors.initials: P
authors.lastname: Teo
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.forename: Marylène
authors.initials: M
authors.lastname: Leboeuf
authors.forename: Donovan
authors.initials: D
authors.lastname: Low
authors.forename: Guillaume
authors.initials: G
authors.lastname: Oller
authors.forename: Francisca
authors.initials: F
authors.lastname: Almeida
authors.forename: Sharon H Y
authors.initials: SH
authors.lastname: Choy
authors.forename: Marcos
authors.initials: M
authors.lastname: Grisotto
authors.forename: Laurent
authors.initials: L
authors.lastname: Renia
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.forename: Igor M
authors.initials: IM
authors.lastname: Samokhvalov
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
mesh_terms: D000367:Age Factors; D000818:Animals; D019070:Cell Lineage; D005260:Female; D007801:Langerhans Cells / Q000166:cytology*; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology; D009000:Monocytes; D023461:Myeloid Progenitor Cells; D011247:Pregnancy; D012867:Skin / Q000166:cytology / Q000196:embryology; D013234:Stem Cells; D015017:Yolk Sac / Q000166:cytology* / Q000196:embryology*