The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways.
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, using a highly efficient xenotransplantation 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 nonobese diabetic-severe combined immunodeficiency (NOD-scid)/IL2rgamma(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.
Research Unit for Human Disease Model, Rikagaku Kenkyusho (RIKEN) Research Center for Allergy and Immunology, Yokohama, Japan.
Fumihiko
F
Ishikawa
Hiroaki
H
Niiro
Tadafumi
T
Iino
Shuro
S
Yoshida
Noriyuki
N
Saito
Shinya
S
Onohara
Toshihiro
T
Miyamoto
Hiroko
H
Minagawa
Shin-Ichiro
S
Fujii
Leonard D
LD
Shultz
Mine
M
Harada
Koichi
K
Akashi
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007231:Infant, Newborn; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000502:physiology