Dataset Information

A Systems-Level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells

ABSTRACT: Mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with regenerative, secretory and immunomodulatory capabilities that are beneficial for the treatment of various diseases. To avoid the issues that come with using tissue-derived MSCs in therapy, MSCs may be generated by the differentiation of human embryonic stems cells (hESCs) in culture. However, the changes that occur during the differentiation process have not been comprehensively characterized. Here, we combined transcriptome, proteome and phosphoproteome profiling to perform an in-depth, multi-omics study of the hESCs-to-MSCs differentiation process. Based on RNA-to-protein correlation, we determined a set of high confidence genes that are important to differentiation. Among the earliest and strongest induced proteins with extensive differential phosphorylation was AHNAK, which we hypothesized to be a defining factor in MSC biology. We observed two distinct expression waves of developmental HOX genes and an AGO2-to-AGO3 switch in gene silencing. Exploring the kinetic of non-coding ORFs during differentiation, we mapped new functions to well annotated long non-coding RNAs (CARMN, MALAT, NEAT1, LINC00152) as well as new candidates which we identified to be important to the differentiation process. Phosphoproteome analysis revealed ESC and MSC-specific phosphorylation motifs with PAK2 and RAF1 as top predicted upstream kinases in MSCs. Our data represent a rich systems-level resource on ESC-to-MSC differentiation that will be useful for the study of stem cell biology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Mesenchymal Cell, Embryonic Stem Cell

SUBMITTER: Johannes Graumann

LAB HEAD: Johannes Graumann

PROVIDER: PXD004652 | Pride | 2019-07-23

REPOSITORIES: Pride

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			Action	DRS
	20140622_QEP_ANB_ESCMSC_OG1_Sample01.raw	Raw
	20140622_QEP_ANB_ESCMSC_OG1_Sample02.raw	Raw
	20140622_QEP_ANB_ESCMSC_OG1_Sample03.raw	Raw
	20140622_QEP_ANB_ESCMSC_OG1_Sample04.raw	Raw
	20140622_QEP_ANB_ESCMSC_OG1_Sample05.raw	Raw

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A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells.

Billing Anja M AM Dib Shaima S SS Bhagwat Aditya M AM da Silva Israel T IT Drummond Rodrigo D RD Hayat Shahina S Al-Mismar Rasha R Ben-Hamidane Hisham H Goswami Neha N Engholm-Keller Kasper K Larsen Martin R MR Suhre Karsten K Rafii Arash A Graumann Johannes J

Molecular & cellular proteomics : MCP 20190722 10

Mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with regenerative, secretory and immunomodulatory capabilities that are beneficial for the treatment of various diseases. To avoid the issues that come with using tissue-derived MSCs in therapy, MSCs may be generated by the differentiation of human embryonic stems cells (hESCs) in culture. However, the changes that occur during the differentiation process have not been comprehensively characterized. Here, we combined trans ...[more]

PMID: 31332097

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