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

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 Gutierrez Gonzalez, Laurence M Brill, Evan Y Snyder

Onderzoeksoutput: Articlepeer review

29 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)527-542
Aantal pagina's16
TijdschriftStem Cell Reports
Volume7
Nummer van het tijdschrift3
DOI's
StatusPublished - 13 sep 2016

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