Flk2+ myeloid progenitors are the main source of Langerhans cells.

Stanford Blood Center, 3373 Hillview Ave, Palo Alto, CA 94304, USA.
Blood (Impact Factor: 9.78). 03/2006; 107(4):1383-90. DOI: 10.1182/blood-2005-05-1878
Source: PubMed

ABSTRACT Langerhans cells (LCs) are antigen-presenting cells (APCs) residing in the epidermis that play a major role in skin immunity. Our earlier studies showed that when skin is inflamed LCs are replaced by bone marrow-derived progenitor cells, while during steady-state conditions LCs are able to self-renew in the skin. Identification of the LC progenitors in bone marrow would represent a critical step toward identifying the factors that regulate LC generation as well as their trafficking to the skin. To determine LC lineage origin, we reconstituted lethally irradiated CD45.2 mice with rigorously purified lymphoid and myeloid progenitors from CD45.1 congenic mice. Twenty-four hours later, we exposed the mice to UV light to deplete resident LCs and induce their replacement by progenitors. Reconstitution with common myeloid progenitors (CMPs), common lymphoid progenitors (CLPs), granulocyte-macrophage progenitors (GMPs), or early thymic progenitors led to LC generation within 2 to 3 weeks. CMPs were at least 20 times more efficient at generating LCs than CLPs. LCs from both lineages were derived almost entirely from fetal liver kinase-2+ (Flk-2+) progenitors, displayed typical dendritic-cell (DC) morphology, and showed long-term persistence in the skin. These results indicate that LCs are derived mainly from myeloid progenitors and are dependent on Flt3-ligand for their development.

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    ABSTRACT: Abstract In this chapter we summarize recent progress in the characterization of different skin stem cell populations and their roles in epidermis, hair follicle, and sweat gland regeneration during homeostasis and injury. We discuss new discoveries in the differentiation capabilities of both embryonic stem cells and induced pluripotent stem cells into functional keratinocytes, with their potential to regenerate skin. We also review how different skin stem cell populations integrate their regulation by intrinsic and extrinsic mechanisms. Furthermore, we discuss a new intrinsic layer of feedback that regulates stem cells in a cell-autonomous manner that, together with newly discovered stem cell niche components, creates a unique environment to host and maintain proper skin stem cell characteristics. These exciting advances in skin stem cells and stem cell niches have helped unravel new concepts in basic stem cell biology and have great translational potential to considerably impact regenerative medicine. Significantly, fully understanding the niche composition and the signals within the microenvironment will help accelerate the design of effective therapeutic strategies to promote stem cell self-renewal and stem cell–based therapies for the regeneration of functional skin with associated skin appendages after injury or in human inherited skin diseases.
    Translational Regenerative Medicine, Edited by Atala, Anthony and Allickson, Julie G, 01/2015: pages 269-292; Academic Press., ISBN: 9780124103962
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