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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3591-3660.
Prepublished online as a Blood First Edition Paper on July 30, 2007; DOI 10.1182/blood-2007-02-071613.
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Submitted February 5, 2007
Accepted July 2, 2007
The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways
Fumihiko Ishikawa, Hiroaki Niiro, Tadafumi Iino, Shuro Yoshida, Noriyuki Saito, Shinya Onohara, Toshihiro Miyamoto, Hiroko Minagawa, Shin-ichiro Fujii, Leonard D Shultz, Mine Harada, and Koichi Akashi*
Research Unit for Human Disease Model, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Division of Microbiology, Aichi Prefectural Institute of Public Health, Nagoya, Japan
Research Unit for Cellular Immunotherapy, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
The Jackson Laboratory, Bar Harbor, ME, United States
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, United States
* Corresponding author; email: akashi{at}cancer.med.kyushu-u.ac.jp.
Two distinct dendritic cell (DC) subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs) have been shown to develop via either the myeloid or the lymphoid pathway in murine hematopoiesis. Lineage-specific phenotypes or functions of "myeloid" and "lymphoid" DCs, however, still remain elusive. Furthermore, such analysis has been particularly difficult in humans, due to lack of an assay system appropriate for the analysis of human stem and progenitor cell differentiation. Here, utilizing a highly efficient xenotransplant model, we extensively analyze the origin and the molecular signature of human DCs. Purified human common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs) were intravenously transplanted into NOD-scid/IL2r null newborn mice. CMPs and CLPs displayed significant expansion in the xenogeneic host, and human cDC and pDC progeny were isolatable. Strikingly, each human DC subset possessed indistinguishable expression patterns of surface phenotype and gene transcripts regardless of their CMP or CLP origin, even at the genome-wide level. Thus, cDC and pDC normally develop after cells have committed to the myeloid or the lymphoid lineage in human hematopoiesis, while their transcriptional signatures are well preserved irrespective of their lineage origin. We propose that human DCs use unique and flexible developmental programs that cannot be categorized into the conventional myeloid or lymphoid pathway.
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