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Secretome profile of living constructs assembled from cell-to-cell crosslinking of human adipose tissue-derived mesenchymal stromal cells

ABSTRACT: We report proteomic data from living constructs assembled entirely from human cells covalently tethered via interfacial bridges with a glycosaminoglycan. Here, bioorthogonal azide groups are installed in cell surface glycoproteins via metabolic glycoengineering, allowing for catalyst-free click-chemistry coupling with a complementary hyaluronan biopolymer. This cell-to-cell tethering strategy enables the use of human cells as active crosslinkers and main building blocks of macroscale, tissue-dense living materials. In light of this, we explore the secretome profile of these constructs following a maturation period of 3 days. Bioinformatic analysis and matrisome annotation revealed the presence of a wide range of proteins related to extracellular matrix organization, assembly and remodeling, as well as proteins involved in cell signaling and migration. These findings highlight the potential of this cell-to-cell tethering strategy for creating nascent living tissue mimetics that can be explored in tissue engineering and regenerative medicine endeavors.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Mesenchymal Stem Cell Of Adipose

DISEASE(S): Wounds And Injuries

SUBMITTER: Rui Vitorino

LAB HEAD: Joao Mano

PROVIDER: PXD042343 | Pride | 2024-07-25

REPOSITORIES: Pride

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Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series

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Secretome profile of living constructs assembled from cell-to-cell crosslinking of human adipose tissue-derived mesenchymal stromal cells

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