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, Koichi Akashi

研究成果: ジャーナルへの寄稿学術誌査読

91 被引用数 (Scopus)

抄録

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)/IL2rγnull 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.

本文言語英語
ページ(範囲)3591-3600
ページ数10
ジャーナルBlood
110
10
DOI
出版ステータス出版済み - 11月 15 2007

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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