Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region

被引:191
作者
Ivanovs, Andrejs [1 ]
Rybtsov, Stanislav [1 ]
Welch, Lindsey [3 ]
Anderson, Richard A. [2 ]
Turner, Marc L. [1 ,4 ]
Medvinsky, Alexander [1 ]
机构
[1] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland
[2] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh EH16 4TJ, Midlothian, Scotland
[3] Univ Strathclyde, Ctr Forens Sci, Glasgow G1 1XW, Lanark, Scotland
[4] Scottish Natl Blood Transfus Serv, Edinburgh EH17 7QT, Midlothian, Scotland
基金
英国惠康基金; 英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
HUMAN EMBRYO; AGM REGION; YOLK-SAC; IN-VIVO; MOUSE EMBRYO; BONE-MARROW; QUANTITATIVE ASSAY; PERIPHERAL-BLOOD; XENOGRAFT MODEL; HUMAN PLACENTA;
D O I
10.1084/jem.20111688
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and only later appear in the yolk sac, liver, and placenta. AGM region cells transplanted into immunodeficient mice provide long-term high level multilineage hematopoietic repopulation. Human AGM region HSCs, although present in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates at least 300 daughter HSCs in primary recipients, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine.
引用
收藏
页码:2417 / 2427
页数:11
相关论文
共 53 条
[1]  
[Anonymous], 2001, HUMAN EMBRYOLOGY TER
[2]   RETRACTED: The human placenta is a hematopoietic organ during the embryonic and fetal periods of development (Retracted Article) [J].
Barcena, Alicia ;
Kapidzic, Mirhan ;
Muench, Marcus O. ;
Gormley, Matthew ;
Scott, Marvin A. ;
Weier, Jingly F. ;
Ferlatte, Christy ;
Fisher, Susan J. .
DEVELOPMENTAL BIOLOGY, 2009, 327 (01) :24-33
[3]   Haematopoietic stem cells derive directly from aortic endothelium during development [J].
Bertrand, Julien Y. ;
Chi, Neil C. ;
Santoso, Buyung ;
Teng, Shutian ;
Stainier, Didier Y. R. ;
Traver, David .
NATURE, 2010, 464 (7285) :108-U120
[4]   Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice [J].
Bhatia, M ;
Wang, JCY ;
Kapp, U ;
Bonnet, D ;
Dick, JE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5320-5325
[6]   In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium [J].
Boisset, Jean-Charles ;
van Cappellen, Wiggert ;
Andrieu-Soler, Charlotte ;
Galjart, Niels ;
Dzierzak, Elaine ;
Robin, Catherine .
NATURE, 2010, 464 (7285) :116-U131
[7]   Kinetic evidence of the regeneration of multilineage hematopoiesis from primitive cells in normal human bone marrow transplanted into immunodeficient mice [J].
Cashman, JD ;
Lapidot, T ;
Wang, JCY ;
Doedens, M ;
Shultz, LD ;
Lansdorp, P ;
Dick, JE ;
Eaves, CJ .
BLOOD, 1997, 89 (12) :4307-4316
[8]   The replication rate of human hematopoietic stem cells in vivo [J].
Catlin, Sandra N. ;
Busque, Lambert ;
Gale, Rosemary E. ;
Guttorp, Peter ;
Abkowitz, Janis L. .
BLOOD, 2011, 117 (17) :4460-4466
[9]   Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice [J].
Conneally, E ;
Cashman, J ;
Petzer, A ;
Eaves, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (18) :9836-9841
[10]   Validation of the AMPFlSTR® SGM Plus™ system for use in forensic casework [J].
Cotton, EA ;
Allsop, RF ;
Guest, JL ;
Frazier, RRE ;
Koumi, P ;
Callow, IP ;
Seager, A ;
Sparkes, RL .
FORENSIC SCIENCE INTERNATIONAL, 2000, 112 (2-3) :151-161