Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium.
The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental and genomic analyses of 58 iPSC from ten laboratories generated using a variety of reprogramming genes, vectors, and cells. Associated global molecular characterization studies identified functionally informative correlations in gene expression, DNA methylation, and/or copy-number variation among key developmental and oncogenic regulators as a result of donor, sex, line stability, reprogramming technology, and cell of origin. Furthermore, X-chromosome inactivation in PSC produced highly correlated differences in teratoma-lineage staining and regulator expression upon differentiation. All experimental results, and raw, processed, and metadata from these analyses, including powerful tools, are interactively accessible from a new online portal at https://www.synapse.org to serve as a reusable resource for the stem cell community.
Department of Biomedical Informatics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Nathan
N
Salomonis
Department of Biomedical Informatics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Phillip J
PJ
Dexheimer
Sage Bionetworks, Seattle, WA 98109, USA.
Larsson
L
Omberg
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Robin
R
Schroll
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Stacy
S
Bush
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA.
Jeffrey
J
Huo
Department of Epidemiology and Public Health, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Lynn
L
Schriml
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Shannan
S
Ho Sui
Division of Human Genetics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Mehdi
M
Keddache
Division of Developmental Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Christopher
C
Mayhew
Division of Pathology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Shiva Kumar
SK
Shanmukhappa
Division of Developmental Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
James
J
Wells
Sage Bionetworks, Seattle, WA 98109, USA.
Kenneth
K
Daily
Sage Bionetworks, Seattle, WA 98109, USA.
Shane
S
Hubler
Computational Biology Program, Oregon Health & Science University, Portland, OR 97239, USA.
Yuliang
Y
Wang
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA.
Elias
E
Zambidis
Sage Bionetworks, Seattle, WA 98109, USA; Computational Biology Program, Oregon Health & Science University, Portland, OR 97239, USA.
Adam
A
Margolin
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Winston
W
Hide
Division of Cardiovascular Medicine, Departments of Medicine and Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Antonis K
AK
Hatzopoulos
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Punam
P
Malik
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA; Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Jose A
JA
Cancelas
Department of Biomedical Informatics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Bruce J
BJ
Aronow
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA; Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH 45229, USA. Electronic address: carolyn.lutzko@cchmc.org.
Carolyn
C
Lutzko
D002454:Cell Differentiation / Q000235:genetics*; D065150:Cellular Reprogramming; D019175:DNA Methylation / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D013234:Stem Cells / Q000378:metabolism