RRC ID 70690
著者 Hayashi Y, Kawabata KC, Tanaka Y, Uehara Y, Mabuchi Y, Murakami K, Nishiyama A, Kiryu S, Yoshioka Y, Ota Y, Sugiyama T, Mikami K, Tamura M, Fukushima T, Asada S, Takeda R, Kunisaki Y, Fukuyama T, Yokoyama K, Uchida T, Hagihara M, Ohno N, Usuki K, Tojo A, Katayama Y, Goyama S, Arai F, Tamura T, Nagasawa T, Ochiya T, Inoue D, Kitamura T.
タイトル MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis.
ジャーナル Cell Rep
Abstract 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.
巻・号 39(6)
ページ 110805
公開日 2022-5-10
DOI 10.1016/j.celrep.2022.110805
PII S2211-1247(22)00572-1
PMID 35545056
MeSH Animals Extracellular Vesicles* / metabolism Hematopoiesis Hematopoietic Stem Cells / metabolism Mesenchymal Stem Cells* / metabolism Mice Myelodysplastic Syndromes* / metabolism
IF 8.109
リソース情報
ヒト・動物細胞 10T1/2(RCB0247) MSC-R37(HMS0020)