Dynamic proteome profiling of human pluripotent stem cell-derived pancreatic progenitors

Author:

Loo Larry Sai Weng12,Vethe Heidrun34,Soetedjo Andreas Alvin Purnomo1,Paulo Joao A.5,Jasmen Joanita1,Jackson Nicholas3ORCID,Bjørlykke Yngvild4,Valdez Ivan A.3,Vaudel Marc6,Barsnes Harald46,Gygi Steven P.5,Ræder Helge47,Teo Adrian Kee Keong128ORCID,Kulkarni Rohit N.3ORCID

Affiliation:

1. Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore

2. School of Biological Sciences, Nanyang Technological University (NTU), Singapore

3. Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts

4. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway

5. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts

6. Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway

7. Department of Pediatrics, Haukeland University Hospital, Bergen, Norway

8. Departments of Biochemistry and Medicine, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore

Abstract

Abstract A comprehensive characterization of the molecular processes controlling cell fate decisions is essential to derive stable progenitors and terminally differentiated cells that are functional from human pluripotent stem cells (hPSCs). Here, we report the use of quantitative proteomics to describe early proteome adaptations during hPSC differentiation toward pancreatic progenitors. We report that the use of unbiased quantitative proteomics allows the simultaneous profiling of numerous proteins at multiple time points, and is a valuable tool to guide the discovery of signaling events and molecular signatures underlying cellular differentiation. We also monitored the activity level of pathways whose roles are pivotal in the early pancreas differentiation, including the Hippo signaling pathway. The quantitative proteomics data set provides insights into the dynamics of the global proteome during the transition of hPSCs from a pluripotent state toward pancreatic differentiation.

Funder

Agency for Science, Technology and Research

Inger R. Haldorsens legat

Norsk Endokrinologisk forenings reisestipend

Novo Nordisk Foundation

Bergen Research Foundation

Diabetesforbundet

Western Norway Regional Health Authority

U.S. National Institutes of Health

Harvard Stem Cell Institute

NIH/NIDDK

National Institutes of Health

Novo Nordisk Fonden

Bergens Forskningsstiftelse

Helse Vest

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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