Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells

被引:206
作者
Boiers, Charlotta [1 ,2 ]
Carrelha, Joana [3 ]
Lutteropp, Michael [3 ]
Luc, Sidinh [3 ]
Green, Joanna C. A. [3 ]
Azzoni, Emanuele [4 ]
Woll, Petter S. [3 ]
Mead, Adam J. [3 ]
Hultquist, Anne [1 ]
Swiers, Gemma [4 ]
Perdiguero, Elisa Gomez [5 ]
Macaulay, Iain C. [3 ]
Melchiori, Luca [3 ]
Luis, Tiago C. [3 ]
Kharazi, Shabnam [1 ]
Bouriez-Jones, Tiphaine [3 ]
Deng, Qiaolin [6 ]
Ponten, Annica [7 ]
Atkinson, Deborah [3 ]
Jensen, Christina T. [3 ]
Sitnicka, Ewa [1 ]
Geissmann, Frederic [5 ]
Godin, Isabelle [8 ]
Sandberg, Rickard [6 ]
de Bruijn, Marella F. T. R. [4 ]
Jacobsen, Sten Eirik W. [3 ,4 ,9 ,10 ]
机构
[1] Lund Univ, Lund Stem Cell Ctr, Haematopoiet Stem Cell Lab, S-22184 Lund, Sweden
[2] Lund Univ, Lund Stem Cell Ctr, S-22184 Lund, Sweden
[3] Univ Oxford, Haematopoiet Stem Cell Lab, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England
[4] Univ Oxford, MRC Mol Haematol Unit, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England
[5] Kings Coll London, Div Immunol Infect & Inflammatory Dis, Ctr Mol & Cellular Biol Inflammat, London SE1 1UL, England
[6] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
[7] Lund Univ, Lund Stem Cell Ctr, Cardiovasc Grp, S-22184 Lund, Sweden
[8] Univ Paris 11, INSERM 1009, Inst Natl Sante & Rech Med, F-94805 Villejuif, France
[9] Karolinska Inst, Dept Cell & Mol Biol, Wallenberg Inst Regenerat Med, S-17177 Stockholm, Sweden
[10] Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, S-17177 Stockholm, Sweden
基金
英国医学研究理事会; 瑞典研究理事会;
关键词
T-CELL; B-CELL; BONE-MARROW; AGM REGION; YOLK-SAC; MULTIPOTENT PROGENITORS; LYMPHOID PROGENITORS; LINEAGE COMMITMENT; FETAL LIVER; MOUSE;
D O I
10.1016/j.stem.2013.08.012
中图分类号
Q813 [细胞工程];
学科分类号
摘要
In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the embryonic lymphoid commitment process initiates earlier than previously appreciated, prior to emergence of definitive HSCs, through establishment of a previously unrecognized entirely immune-restricted and lymphoid-primed progenitor. Notably, this immune-restricted progenitor appears to first emerge in the yolk sac and contributes physiologically to the establishment of lymphoid and some myeloid components of the immune-system, establishing the lymphomyeloid lineage restriction process as an early and physiologically important line-age-commitment step in mammalian hematopoiesis.
引用
收藏
页码:535 / 548
页数:14
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