Computational image analysis of colony and nuclear morphology to evaluate human induced pluripotent stem cells.
Non-invasive evaluation of cell reprogramming by advanced image analysis is required to maintain the quality of cells intended for regenerative medicine. Here, we constructed living and unlabelled colony image libraries of various human induced pluripotent stem cell (iPSC) lines for supervised machine learning pattern recognition to accurately distinguish bona fide iPSCs from improperly reprogrammed cells. Furthermore, we found that image features for efficient discrimination reside in cellular components. In fact, extensive analysis of nuclear morphologies revealed dynamic and characteristic signatures, including the linear form of the promyelocytic leukaemia (PML)-defined structure in iPSCs, which was reversed to a regular sphere upon differentiation. Our data revealed that iPSCs have a markedly different overall nuclear architecture that may contribute to highly accurate discrimination based on the cell reprogramming status.
1] Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan [2] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
Kazuaki
K
Tokunaga
1] Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan [2] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
Noriko
N
Saitoh
Image Informatics and Computational Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
Ilya G
IG
Goldberg
Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Chiyomi
C
Sakamoto
Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Yoko
Y
Yasuda
Center for iPS Cell Research and Application, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Yoshinori
Y
Yoshida
1] Center for iPS Cell Research and Application, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan [2] Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Shinya
S
Yamanaka
1] Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan [2] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
Mitsuyoshi
M
Nakao
D001185:Artificial Intelligence; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D065150:Cellular Reprogramming / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000648:ultrastructure*; D057054:Molecular Imaging; D010363:Pattern Recognition, Automated / Q000706:statistics & numerical data*