Dataset Information

Samon_1803_DIA_HSPC - Sensitive quantitative proteomics of human hematopoietic stem and progenitor cells by data-independent acquisition mass spectrometry

ABSTRACT: - tryptic digests of CD34+ FAC-sorted cells dilution series acquired in DIA mode on Orbitrap Lumos - tryptic digests of HSC, MEP, GMP, CMP FAC-sorted cells acquired in DIA mode on Orbitrap Lumos

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hematopoietic Stem Cell, Haematopoietic Stem Cells

SUBMITTER: Ludovic Gillet

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD009255 | Pride | 2019-04-25

REPOSITORIES: Pride

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Publications

Sensitive Quantitative Proteomics of Human Hematopoietic Stem and Progenitor Cells by Data-independent Acquisition Mass Spectrometry.

Amon Sabine S Meier-Abt Fabienne F Gillet Ludovic C LC Dimitrieva Slavica S Theocharides Alexandre P A APA Manz Markus G MG Aebersold Ruedi R

Molecular & cellular proteomics : MCP 20190411 7

Physiological processes in multicellular organisms depend on the function and interactions of specialized cell types operating in context. Some of these cell types are rare and thus obtainable only in minute quantities. For example, tissue-specific stem and progenitor cells are numerically scarce, but functionally highly relevant, and fulfill critical roles in development, tissue maintenance, and disease. Whereas low numbers of cells are routinely analyzed by genomics and transcriptomics, corres ...[more]

PMID: 30975897

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Project description:The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100Ã-verbB;Trp53. In this glioma model, CSCs are enriched in the side-population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared to non-SP cells from the same tumors. Furthermore, gene expression analysis comparing FACS-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human GBM (glioblatoma multiforme) cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the cancer stem cell hypothesis. Experiment Overall Design: This study features two factors, injected cell origin (either tumorsphere or neurosphere) and FACS cell population (either side population or non-side population cells). There were two different tumorspheres, labeled 3447 and 4346 that were isolated from brain tumors in S100beta-verbB;p53-/- or S100beta-verbB;p53+/- mice. The tumorspheres were injected separately into the brains of NOD.Cg-Prkdc<scid>Il2rg<tm1Wjl>/SzJ mice to generate biological triplicates of each primary tumor. Tumorspheres were isolated and cultured before FACS sorting to obtain side population and non-side population cells. As a control, untransformed neurospheres from three independent S100beta-verbB;p53-/- or S100beta-verbB;p53+/- mice were isolated, cultured, and FACS sorted to obtain side population and non-side population cells. Side population and non-side population cells cultured from three mice injected with the 3447 cultured tumorspheres were assayed for gene expression (six samples). Side-population stem cells cultured from three mice injected with the 4346 cultured tumorspheres were assayed for gene expression (three samples). Side-population and non-side population cells cultured from three mice injected with the neurospheres were assayed for gene expression (six samples).

Dataset Information

Samon_1803_DIA_HSPC - Sensitive quantitative proteomics of human hematopoietic stem and progenitor cells by data-independent acquisition mass spectrometry

Publications

Sensitive Quantitative Proteomics of Human Hematopoietic Stem and Progenitor Cells by Data-independent Acquisition Mass Spectrometry.

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