Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages

Guillaume Hoeffel, Yilin Wang, Melanie Greter, Peter See, Pearline Teo, Benoit Malleret, Marylène Leboeuf, Donovan Low, Guillaume Oller, Francisca Almeida, Sharon H Y Choy, Marcos Grisotto, Laurent Renia, Simon Conway, E. Richard Stanley, Jerry K Y Chan, Lai Guan Ng, Igor M. Samokhvalov, Miriam Merad, Florent Ginhoux

Research output: Contribution to journalArticle

359 Citations (Scopus)

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 monocytederived 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.

Original languageEnglish
Pages (from-to)1167-1181
Number of pages15
JournalJournal of Experimental Medicine
Volume209
Issue number6
DOIs
StatePublished - Jun 4 2012

Fingerprint

Yolk Sac
Langerhans Cells
Monocytes
Macrophages
Liver
Skin
Dendritic Cells
Seeds
Hematopoiesis
Microglia
Fetal Development
Epidermis
Embryonic Development
Embryonic Structures
Parturition
Brain

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. / Hoeffel, Guillaume; Wang, Yilin; Greter, Melanie; See, Peter; Teo, Pearline; Malleret, Benoit; Leboeuf, Marylène; Low, Donovan; Oller, Guillaume; Almeida, Francisca; Choy, Sharon H Y; Grisotto, Marcos; Renia, Laurent; Conway, Simon; Stanley, E. Richard; Chan, Jerry K Y; Ng, Lai Guan; Samokhvalov, Igor M.; Merad, Miriam; Ginhoux, Florent.

In: Journal of Experimental Medicine, Vol. 209, No. 6, 04.06.2012, p. 1167-1181.

Research output: Contribution to journalArticle

Hoeffel, G, Wang, Y, Greter, M, See, P, Teo, P, Malleret, B, Leboeuf, M, Low, D, Oller, G, Almeida, F, Choy, SHY, Grisotto, M, Renia, L, Conway, S, Stanley, ER, Chan, JKY, Ng, LG, Samokhvalov, IM, Merad, M & Ginhoux, F 2012, 'Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages', Journal of Experimental Medicine, vol. 209, no. 6, pp. 1167-1181. https://doi.org/10.1084/jem.20120340
Hoeffel, Guillaume ; Wang, Yilin ; Greter, Melanie ; See, Peter ; Teo, Pearline ; Malleret, Benoit ; Leboeuf, Marylène ; Low, Donovan ; Oller, Guillaume ; Almeida, Francisca ; Choy, Sharon H Y ; Grisotto, Marcos ; Renia, Laurent ; Conway, Simon ; Stanley, E. Richard ; Chan, Jerry K Y ; Ng, Lai Guan ; Samokhvalov, Igor M. ; Merad, Miriam ; Ginhoux, Florent. / Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 6. pp. 1167-1181.
@article{491d9f4818d9408cb965cb32b0de2925,
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 monocytederived 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.",
author = "Guillaume Hoeffel and Yilin Wang and Melanie Greter and Peter See and Pearline Teo and Benoit Malleret and Maryl{\`e}ne Leboeuf and Donovan Low and Guillaume Oller and Francisca Almeida and Choy, {Sharon H Y} and Marcos Grisotto and Laurent Renia and Simon Conway and Stanley, {E. Richard} and Chan, {Jerry K Y} and Ng, {Lai Guan} and Samokhvalov, {Igor M.} and Miriam Merad and Florent Ginhoux",
year = "2012",
month = "6",
day = "4",
doi = "10.1084/jem.20120340",
language = "English",
volume = "209",
pages = "1167--1181",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages

AU - Hoeffel, Guillaume

AU - Wang, Yilin

AU - Greter, Melanie

AU - See, Peter

AU - Teo, Pearline

AU - Malleret, Benoit

AU - Leboeuf, Marylène

AU - Low, Donovan

AU - Oller, Guillaume

AU - Almeida, Francisca

AU - Choy, Sharon H Y

AU - Grisotto, Marcos

AU - Renia, Laurent

AU - Conway, Simon

AU - Stanley, E. Richard

AU - Chan, Jerry K Y

AU - Ng, Lai Guan

AU - Samokhvalov, Igor M.

AU - Merad, Miriam

AU - Ginhoux, Florent

PY - 2012/6/4

Y1 - 2012/6/4

N2 - 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 monocytederived 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.

AB - 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 monocytederived 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.

UR - http://www.scopus.com/inward/record.url?scp=84864298329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864298329&partnerID=8YFLogxK

U2 - 10.1084/jem.20120340

DO - 10.1084/jem.20120340

M3 - Article

VL - 209

SP - 1167

EP - 1181

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 6

ER -