Rapid and dynamic alterations of gene expression profiles of adult porcine bone marrow-derived stem cell in response to hypoxia.
This study sought to identify the gene expression patterns of porcine bone marrow-derived MSC in response to hypoxia and to investigate novel specific hypoxic targets that may have a role in determining MSC proliferation/survival and differentiation. MSC from 15 animals were incubated in 1% oxygen and 8% carbon dioxide for 6, 12, and 24 h. RNA samples were isolated and assayed with Affymetrix porcine arrays and quantitative reverse-transcription PCR. Significant gene expression levels among the four groups of normoxia, 6-, 12-, and 24-h hypoxia were identified. The pattern in the 12-h hypoxia group was similar to that of the 24-h group. Of 23,924 probes, 377 and 210 genes were regulated in the 6- and 24-h hypoxia groups, respectively. Functional classification of the hypoxic regulated genes was mainly clustered in cell proliferation and response to stress. However, the major upregulated genes in the 6-h group were activated in cell cycle phases; the genes in the 24-h hypoxia were evenly separated into cell differentiation, apoptosis, and cellular metabolic processes. Twenty-eight genes were upregulated in all hypoxia groups; these genes are considered as hypoxic targets. Our results identified a genome-wide hypoxia-induced gene expression pattern in porcine MSC. This study provides a global view of molecular events in the cells during exposure to hypoxia and revealed a set of novel candidate hypoxic targets.
Wang
Suna
S
Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. wangs3@mail.nih.gov
Zhou
Yifu
Y
Seavey
Caleb N
CN
Singh
Avneesh K
AK
Xu
Xiuli
X
Hunt
Timothy
T
Hoyt
Robert F
RF
Horvath
Keith A
KA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine