MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis
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 t...
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| Veröffentlicht in: | Cell reports (Cambridge) 2022-05, Vol.39 (6), p.110805-110805, Article 110805 |
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| creator | Hayashi, Yasutaka Kawabata, Kimihito C Tanaka, Yosuke Uehara, Yasufumi Mabuchi, Yo Murakami, Koichi Nishiyama, Akira Kiryu, Shigeru Yoshioka, Yusuke Ota, Yasunori Sugiyama, Tatsuki Mikami, Keiko Tamura, Moe Fukushima, Tsuyoshi Asada, Shuhei Takeda, Reina Kunisaki, Yuya Fukuyama, Tomofusa Yokoyama, Kazuaki Uchida, Tomoyuki Hagihara, Masao Ohno, Nobuhiro Usuki, Kensuke Tojo, Arinobu Katayama, Yoshio Goyama, Susumu Arai, Fumio Tamura, Tomohiko Nagasawa, Takashi Ochiya, Takahiro Inoue, Daichi Kitamura, Toshio |
| description | 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. |
| doi_str_mv | 10.1016/j.celrep.2022.110805 |
| format | Article |
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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. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-f5ee004b9654748f198ab16cef24b79ae45da54a123844cba7398ef5a81e91603</citedby><cites>FETCH-LOGICAL-c419t-f5ee004b9654748f198ab16cef24b79ae45da54a123844cba7398ef5a81e91603</cites><orcidid>0000-0001-7855-1767</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,865,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35545056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hayashi, Yasutaka</creatorcontrib><creatorcontrib>Kawabata, Kimihito C</creatorcontrib><creatorcontrib>Tanaka, Yosuke</creatorcontrib><creatorcontrib>Uehara, Yasufumi</creatorcontrib><creatorcontrib>Mabuchi, Yo</creatorcontrib><creatorcontrib>Murakami, Koichi</creatorcontrib><creatorcontrib>Nishiyama, Akira</creatorcontrib><creatorcontrib>Kiryu, Shigeru</creatorcontrib><creatorcontrib>Yoshioka, Yusuke</creatorcontrib><creatorcontrib>Ota, Yasunori</creatorcontrib><creatorcontrib>Sugiyama, Tatsuki</creatorcontrib><creatorcontrib>Mikami, Keiko</creatorcontrib><creatorcontrib>Tamura, Moe</creatorcontrib><creatorcontrib>Fukushima, Tsuyoshi</creatorcontrib><creatorcontrib>Asada, Shuhei</creatorcontrib><creatorcontrib>Takeda, Reina</creatorcontrib><creatorcontrib>Kunisaki, Yuya</creatorcontrib><creatorcontrib>Fukuyama, Tomofusa</creatorcontrib><creatorcontrib>Yokoyama, Kazuaki</creatorcontrib><creatorcontrib>Uchida, Tomoyuki</creatorcontrib><creatorcontrib>Hagihara, Masao</creatorcontrib><creatorcontrib>Ohno, Nobuhiro</creatorcontrib><creatorcontrib>Usuki, Kensuke</creatorcontrib><creatorcontrib>Tojo, Arinobu</creatorcontrib><creatorcontrib>Katayama, Yoshio</creatorcontrib><creatorcontrib>Goyama, Susumu</creatorcontrib><creatorcontrib>Arai, Fumio</creatorcontrib><creatorcontrib>Tamura, Tomohiko</creatorcontrib><creatorcontrib>Nagasawa, Takashi</creatorcontrib><creatorcontrib>Ochiya, Takahiro</creatorcontrib><creatorcontrib>Inoue, Daichi</creatorcontrib><creatorcontrib>Kitamura, Toshio</creatorcontrib><title>MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis</title><title>Cell reports (Cambridge)</title><addtitle>Cell Rep</addtitle><description>Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis and frequent progression to leukemia. 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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.</abstract><cop>United States</cop><pmid>35545056</pmid><doi>10.1016/j.celrep.2022.110805</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-7855-1767</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Extracellular Vesicles - metabolism Hematopoiesis Hematopoietic Stem Cells - metabolism Mesenchymal Stem Cells - metabolism Mice Myelodysplastic Syndromes - metabolism |
| title | MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis |
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