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Published online on May 8, 2006, 10.1073/pnas.0602646103
PNAS | May 16, 2006 | vol. 103 | no. 20 | 7801-7806


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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Multiorgan engraftment and differentiation of human cord blood CD34+Lin cells in goats assessed by gene expression profiling

Fanyi Zeng*, Mei-jue Chen*, Don A. Baldwin{dagger}, Zhi-juan Gong*, Jing-bin Yan*, Hui Qian*, Juan Wang*, Xiaoyan Jiang*,{ddagger},§, Zhao-rui Ren*, Deming Sun*, and Shu-zhen Huang*

*Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, 24/1400 West Beijing Road, Shanghai 200040, People's Republic of China; {dagger}Penn Microarray Facility, University of Pennsylvania, Philadelphia, PA 19104; and {ddagger}Terry Fox Laboratory, British Columbia Cancer Agency and §Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 1L3

Communicated by Jiazhen Tan, Fudan University, Shanghai, People's Republic of China, April 3, 2006 (received for review December 8, 2005)

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 beta2 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.

hematopoietic stem cell | transplantation | plasticity | microarray


Author contributions: F.Z., D.S., and S.-z.H. designed research; F.Z., M.-j.C., D.A.B., Z.-j.G., J.-b.Y., H.Q., J.W., X.J., and S.-z.H. performed research; F.Z., D.A.B., and S.-z.H. contributed new reagents/analytic tools; F.Z., M.-j.C., D.A.B., and S.-z.H. analyzed data; and F.Z., D.A.B., X.J., Z.-r.R., D.S., and S.-z.H. wrote the paper.

Conflict of interest statement: No conflicts declared.

Data deposition: The data described in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GDS1023).

To whom correspondence should be addressed. E-mail: szhuang{at}simg.org or ytzeng{at}stn.sh.cn

© 2006 by The National Academy of Sciences of the USA


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