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Fate changes leading to multipotency of isolated mesenchymal cells [Expression: Dense_vs_Sparse]

ABSTRACT: Mesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGFβ and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues. The gene expression profile of dense and sparse MSC cultures in three sequential days after seeding was compared

ORGANISM(S): Mus musculus

SUBMITTER: Ofer Shoshani

PROVIDER: E-GEOD-48546 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Fate changes leading to multipotency of isolated mesenchymal cells [Expression: Population_vs_Clone]

Project description:Mesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGFβ and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues. The gene expression profile of MSC population was compared with one of its derived single cell clones

2014-03-20 | E-GEOD-48545 | biostudies-arrayexpress

Fate changes leading to multipotency of isolated mesenchymal cells [ChIP-Seq]

Project description:Mesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGFβ and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues. MSC 21 population and one of its derived clones (4L.1.4) were grown to confuence, and IP of fragmented DNA using an antibody directed against H4K20ME1, or non-immune serum (control) was done. Pulled DNA was then sequenced.

2014-03-20 | E-GEOD-48544 | biostudies-arrayexpress

Fate changes leading to multipotency of isolated mesenchymal cells [Expression: Dense_vs_Sparse]

2014-03-20 | GSE48546 | GEO

Fate changes leading to multipotency of isolated mesenchymal cells [Expression: Population_vs_Clone]

2014-03-20 | GSE48545 | GEO

Fate changes leading to multipotency of isolated mesenchymal cells [ChIP-Seq]

2014-03-20 | GSE48544 | GEO

Fate changes leading to multipotency of isolated mesenchymal cells

Project description:Fate changes leading to multipotency of isolated mesenchymal cells

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Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulators of mesenchymal multipotency

Project description:Temporal data on gene expression and context-specific open chromatin states can improve identification of key transcription factors (TFs) and the gene regulatory networks (GRNs) controlling cellular differentiation. However, their integration remains challenging. Here, we delineate a general approach for data-driven and unbiased identification of key TFs and dynamic GRNs, called EPIC-DREM. We generated time-series transcriptomic and epigenomic profiles during differentiation of mouse multipotent bone marrow stromal cells (MSCs) towards adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages and identifed the shared TFs involved in both differentiation processes. To take an alternative approach to prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic MSC-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and we propose they function as guardians of mesenchymal multipotency.

2019-02-07 | E-MTAB-6840 | biostudies-arrayexpress

Single-cell profiling of human adipose tissue-derived mesenchymal progenitor cells induced toward adipogenic fate.

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2023-04-01 | GSE198482 | GEO

Fate changes leading to multipotency of isolated mesenchymal cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-03-20 | E-GEOD-48547 | biostudies-arrayexpress

OCT4-SOX2 dimers reshape the epigenome to promote neural crest multipotency [RNA-Seq]

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2022-09-06 | GSE163768 | GEO

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