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Loss of endothelial membrane KIT ligand affects systemic KIT ligand levels but not bone marrow hematopoietic stem cells.
Matsuoka, Sahoko; Facchini, Raffaella; Luis, Tiago C; Carrelha, Joana; Woll, Petter S; Mizukami, Takuo; Wu, Bishan; Boukarabila, Hanane; Buono, Mario; Norfo, Ruggiero; Arai, Fumio; Suda, Toshio; Mead, Adam J; Nerlov, Claus; Jacobsen, Sten Eirik W.
Afiliação
  • Matsuoka S; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Facchini R; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Luis TC; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Carrelha J; Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom.
  • Woll PS; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Mizukami T; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Wu B; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Boukarabila H; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Buono M; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Norfo R; Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Arai F; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Suda T; Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Mead AJ; Cancer Science Institute, National University of Singapore, Singapore, Singapore.
  • Nerlov C; Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Jacobsen SEW; Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Blood ; 142(19): 1622-1632, 2023 11 09.
Article em En | MEDLINE | ID: mdl-37562000
A critical regulatory role of hematopoietic stem cell (HSC) vascular niches in the bone marrow has been implicated to occur through endothelial niche cell expression of KIT ligand. However, endothelial-derived KIT ligand is expressed in both a soluble and membrane-bound form and not unique to bone marrow niches, and it is also systemically distributed through the circulatory system. Here, we confirm that upon deletion of both the soluble and membrane-bound forms of endothelial-derived KIT ligand, HSCs are reduced in mouse bone marrow. However, the deletion of endothelial-derived KIT ligand was also accompanied by reduced soluble KIT ligand levels in the blood, precluding any conclusion as to whether the reduction in HSC numbers reflects reduced endothelial expression of KIT ligand within HSC niches, elsewhere in the bone marrow, and/or systemic soluble KIT ligand produced by endothelial cells outside of the bone marrow. Notably, endothelial deletion, specifically of the membrane-bound form of KIT ligand, also reduced systemic levels of soluble KIT ligand, although with no effect on stem cell numbers, implicating an HSC regulatory role primarily of soluble rather than membrane KIT ligand expression in endothelial cells. In support of a role of systemic rather than local niche expression of soluble KIT ligand, HSCs were unaffected in KIT ligand deleted bones implanted into mice with normal systemic levels of soluble KIT ligand. Our findings highlight the need for more specific tools to unravel niche-specific roles of regulatory cues expressed in hematopoietic niche cells in the bone marrow.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Células-Tronco / Células Endoteliais Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Células-Tronco / Células Endoteliais Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Reino Unido