Multiorgan engraftment and differentiation of human cord blood CD34+Lin- cells in goats assessed by gene expression profiling

被引:37
作者
Zeng, Fanyi
Chen, Mei-jue
Baldwin, Don A.
Gong, Zhi-juan
Yan, Jing-bin
Qian, Hui
Wang, Juan
Jiang, Xiaoyan
Ren, Zhao-rui
Sun, Deming
Huang, Shu-zhen
机构
[1] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Inst Med Genet, Shanghai 200040, Peoples R China
[2] Univ Penn, Penn Microarray Facil, Philadelphia, PA 19104 USA
[3] Univ British Columbia, British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[4] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1L3, Canada
关键词
hematopoietic stem cell; transplantation; plasticity; microarray;
D O I
10.1073/pnas.0602646103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To investigate multitissue engraftment of human primitive hematopoietic cells and their differentiation in goats, human CD34(+) Lin(-) cord blood cells transduced with a GFP vector were transplanted into fetal goats at 45-55 days of gestation. GFP(+) cells were detected in hematopoietic and nonhematopoietic organs including blood, bone marrow, spleen, liver, kidney, muscle, lung, and heart of the recipient goats (1.2-36% of all cells examined). We identified human beta 2 microglobulin-positive cells in multiple tissues. GFP(+) cells sorted from the perfused liver of a transplant goat showed human insulin-like growth factor 1 gene sequences, indicating that the engrafted GFP(+) cells were of human origin. A substantial fraction of cells engrafted in goat livers expressed the human hepatocyte-specific antigen, proliferating cell nuclear antigen, albumin, hepatocyte nuclear factor, and GFP. DNA content analysis showed no evidence for cellular fusion. Long-term engraftment of GFP(+) cells could be detected in the blood of goats for up to 2 yr. Microarray analysis indicated that human genes from a variety of functional categories were expressed in chimeric livers and blood. The human/goat xenotransplant model provides a unique system to study the kinetics of hematopoietic stem cell engraftment, gene expression, and possible stem cell plasticity under noninjured conditions.
引用
收藏
页码:7801 / 7806
页数:6
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共 32 条
  • [31] In utero transplantation of human hematopoetic stem cells into fetal goats under B-type ultrasonographic scan: an experimental model for the study of potential prenatal therapy
    Zeng, FY
    Chen, MJ
    Huang, WY
    Yan, JB
    Xiao, YP
    Gong, ZJ
    Ren, ZR
    Huang, SZ
    [J]. EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 2005, 118 (02) : 170 - 173
  • [32] Transcript profiling during preimplantation mouse development
    Zeng, FY
    Baldwin, DA
    Schultz, RM
    [J]. DEVELOPMENTAL BIOLOGY, 2004, 272 (02) : 483 - 496