Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profi...

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Main Authors: Ilyas Singec, Andrew M. Crain, Junjie Hou, Brian T.D. Tobe, Maria Talantova, Alicia A. Winquist, Kutbuddin S. Doctor, Jennifer Choy, Xiayu Huang, Esther La Monaca, David M. Horn, Dieter A. Wolf, Stuart A. Lipton, Gustavo J. Gutierrez, Laurence M. Brill, Evan Y. Snyder
Format: Article
Language:English
Published: Elsevier 2016-09-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671116301436
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author Ilyas Singec
Andrew M. Crain
Junjie Hou
Brian T.D. Tobe
Maria Talantova
Alicia A. Winquist
Kutbuddin S. Doctor
Jennifer Choy
Xiayu Huang
Esther La Monaca
David M. Horn
Dieter A. Wolf
Stuart A. Lipton
Gustavo J. Gutierrez
Laurence M. Brill
Evan Y. Snyder
author_facet Ilyas Singec
Andrew M. Crain
Junjie Hou
Brian T.D. Tobe
Maria Talantova
Alicia A. Winquist
Kutbuddin S. Doctor
Jennifer Choy
Xiayu Huang
Esther La Monaca
David M. Horn
Dieter A. Wolf
Stuart A. Lipton
Gustavo J. Gutierrez
Laurence M. Brill
Evan Y. Snyder
author_sort Ilyas Singec
collection DOAJ
description Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt.
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spelling doaj.art-03e02bec095e4ecea0312b9f57adc9322022-12-22T03:31:40ZengElsevierStem Cell Reports2213-67112016-09-017352754210.1016/j.stemcr.2016.07.019Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic ProfilingIlyas Singec0Andrew M. Crain1Junjie Hou2Brian T.D. Tobe3Maria Talantova4Alicia A. Winquist5Kutbuddin S. Doctor6Jennifer Choy7Xiayu Huang8Esther La Monaca9David M. Horn10Dieter A. Wolf11Stuart A. Lipton12Gustavo J. Gutierrez13Laurence M. Brill14Evan Y. Snyder15Center for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAProteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAInformatics and Data Management, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAInformatics and Data Management, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USADepartment of Biology, Vrije Universiteit Brussel, 1050 Brussels, BelgiumThermo Fisher Scientific Inc., San Jose, CA 95134, USAProteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAProteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAControlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt.http://www.sciencedirect.com/science/article/pii/S2213671116301436
spellingShingle Ilyas Singec
Andrew M. Crain
Junjie Hou
Brian T.D. Tobe
Maria Talantova
Alicia A. Winquist
Kutbuddin S. Doctor
Jennifer Choy
Xiayu Huang
Esther La Monaca
David M. Horn
Dieter A. Wolf
Stuart A. Lipton
Gustavo J. Gutierrez
Laurence M. Brill
Evan Y. Snyder
Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
Stem Cell Reports
title Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
title_full Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
title_fullStr Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
title_full_unstemmed Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
title_short Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
title_sort quantitative analysis of human pluripotency and neural specification by in depth phospho proteomic profiling
url http://www.sciencedirect.com/science/article/pii/S2213671116301436
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