MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis

Yasutaka Hayashi, Kimihito C. Kawabata, Yosuke Tanaka, Yasufumi Uehara, Yo Mabuchi, Koichi Murakami, Akira Nishiyama, Shigeru Kiryu, Yusuke Yoshioka, Yasunori Ota, Tatsuki Sugiyama, Keiko Mikami, Moe Tamura, Tsuyoshi Fukushima, Shuhei Asada, Reina Takeda, Yuya Kunisaki, Tomofusa Fukuyama, Kazuaki Yokoyama, Tomoyuki UchidaMasao Hagihara, Nobuhiro Ohno, Kensuke Usuki, Arinobu Tojo, Yoshio Katayama, Susumu Goyama, Fumio Arai, Tomohiko Tamura, Takashi Nagasawa, Takahiro Ochiya, Daichi Inoue, Toshio Kitamura

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis and frequent progression to leukemia. It has long remained unresolved how MDS cells, which are less proliferative, inhibit normal hematopoiesis and eventually dominate the bone marrow space. Despite several studies implicating mesenchymal stromal or stem cells (MSCs), a principal component of the HSC niche, in the inhibition of normal hematopoiesis, the molecular mechanisms underlying this process remain unclear. Here, we demonstrate that both human and mouse MDS cells perturb bone metabolism by suppressing the osteolineage differentiation of MSCs, which impairs the ability of MSCs to support normal HSCs. Enforced MSC differentiation rescues the suppressed normal hematopoiesis in both in vivo and in vitro MDS models. Intriguingly, the suppression effect is reversible and mediated by extracellular vesicles (EVs) derived from MDS cells. These findings shed light on the novel MDS EV-MSC axis in ineffective hematopoiesis.

本文言語English
論文番号110805
ジャーナルCell Reports
39
6
DOI
出版ステータスPublished - 2022 5月 10
外部発表はい

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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