TY - JOUR
T1 - MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis
AU - Hayashi, Yasutaka
AU - Kawabata, Kimihito C.
AU - Tanaka, Yosuke
AU - Uehara, Yasufumi
AU - Mabuchi, Yo
AU - Murakami, Koichi
AU - Nishiyama, Akira
AU - Kiryu, Shigeru
AU - Yoshioka, Yusuke
AU - Ota, Yasunori
AU - Sugiyama, Tatsuki
AU - Mikami, Keiko
AU - Tamura, Moe
AU - Fukushima, Tsuyoshi
AU - Asada, Shuhei
AU - Takeda, Reina
AU - Kunisaki, Yuya
AU - Fukuyama, Tomofusa
AU - Yokoyama, Kazuaki
AU - Uchida, Tomoyuki
AU - Hagihara, Masao
AU - Ohno, Nobuhiro
AU - Usuki, Kensuke
AU - Tojo, Arinobu
AU - Katayama, Yoshio
AU - Goyama, Susumu
AU - Arai, Fumio
AU - Tamura, Tomohiko
AU - Nagasawa, Takashi
AU - Ochiya, Takahiro
AU - Inoue, Daichi
AU - Kitamura, Toshio
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/5/10
Y1 - 2022/5/10
N2 - 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.
AB - 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.
KW - CP: Cancer
KW - CP: Stem cell research
KW - extracellular vesicles
KW - hematopoietic stem cells
KW - mesenchymal stromal/stem cells
KW - microRNAs
KW - myelodysplastic syndrome
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U2 - 10.1016/j.celrep.2022.110805
DO - 10.1016/j.celrep.2022.110805
M3 - Article
C2 - 35545056
AN - SCOPUS:85129691849
SN - 2211-1247
VL - 39
JO - Cell Reports
JF - Cell Reports
IS - 6
M1 - 110805
ER -