Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency
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PROVIDER: PRJNA387263 | ENA |
REPOSITORIES: ENA
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Project description:Recently, we reported that bacterial incorporation induces cellular transdifferentiation of human fibroblasts. However, the bacterium-intrinsic cellular- transdifferentiation factor remained unknown. Here, we found that cellular transdifferentiation is caused by ribosomes. Ribosomes, isolated from both prokaryotic and eukaryotic cells, induce the formation of embryoid body-like cell clusters. Numerous ribosomes are incorporated into both the cytoplasm and nucleus through trypsin-activated endocytosis, which leads to cell-cluster formation. Although ribosome-induced cell clusters (RICs) express several stemness markers and differentiate into derivatives of all three germ layers in heterogeneous cell populations, RICs fail to proliferate, alter the methylation states of pluripotent genes, or contribute to teratoma or chimera formation. However, RICs express markers of epithelial–mesenchymal transition without altering the cell cycle, despite their proliferation obstruction. These findings demonstrate that incorporation of ribosomes into host cells induces cell transdifferentiation and alters cellular plasticity.
2018-01-25 | GSE99053 | GEO
Project description:Recently, we reported that bacterial incorporation induces cellular transdifferentiation of human fibroblasts. However, the bacterium-intrinsic cellular- transdifferentiation factor remained unknown. Here, we found that cellular transdifferentiation is caused by ribosomes. Ribosomes, isolated from both prokaryotic and eukaryotic cells, induce the formation of embryoid body-like cell clusters. Numerous ribosomes are incorporated into both the cytoplasm and nucleus through trypsin-activated endocytosis, which leads to cell-cluster formation. Although ribosome-induced cell clusters (RICs) express several stemness markers and differentiate into derivatives of all three germ layers in heterogeneous cell populations, RICs fail to proliferate, alter the methylation states of pluripotent genes, or contribute to teratoma or chimera formation. However, RICs express markers of epithelial–mesenchymal transition without altering the cell cycle, despite their proliferation obstruction. These findings demonstrate that incorporation of ribosomes into host cells induces cell transdifferentiation and alters cellular plasticity.
2018-01-25 | GSE99088 | GEO
Project description: Not available
| S-EPMC5786109 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-01-25 | GSE99089 | GEO
Project description:Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency [Array]
| PRJNA387153 | ENA
Project description:Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency [RNA-Seq]
| PRJNA387275 | ENA
Project description:Transdifferentiation has been recently described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors (TFs) GATA4, TBX5, MEF2C, MYOCD, NKX2-5, and delivery of microRNAs miR-1 and miR-133a. Cells undergoing transdifferentiation expressed ACTN2 and TNNT2 and partially organized their cytoskeleton in a cross-striated manner. The conversion process was associated with significant upregulation of a cohort of cardiac-specific genes, activation of pathways associated with muscle contraction and physiology, and downregulation of fibroblastic markers. We used a genetically encoded calcium indicator and readily detected active calcium transients although no spontaneous contractions were observed in transdifferentiated cells. Finally, we determined that inhibition of Janus kinase 1, inhibition of glycogen synthase kinase 3, or addition of NRG1 significantly enhanced the efficiency of transdifferentiation. Overall, we describe a method for achieving transdifferentiation of human dermal fibroblasts into induced cardiomyocyte-like cells via transcription factor overexpression, microRNA delivery, and molecular pathway manipulation.
2017-02-08 | GSE81723 | GEO
Project description:Glandular epithelia including the mammary gland (MG) and the prostate are composed of basal cells (BC) and luminal cells (LC). Lineage tracing demonstrates that many glandular epithelia initially develop from multipotent basal stem cells (BaSCs) that are replaced in adult life by distinct pool of unipotent stem cells (SCs). However, adult unipotent BaSC can reactivate multipotency and give rise to LCs upon transplantation or oncogene expression, demonstrating the important plasticity of BaSCs in regenerative and pathological conditions, and suggesting that an active mechanism restricts multipotency in BaSCs during physiological conditions. The nature of this mechanism is currently unknown. Here, we assess whether basal and luminal cell-cell communication restricts multipotency in glandular epithelia. To this end, we performed lineage tracing of BCs together with the ablation of LCs in different adult glandular epithelia including MG, prostate, sweat glands and salivary glands and assessed the fate of BaSCs overtime. Interestingly, ablation of LCs reactivated multipotency in unipotent adult BaSCs from multiple epithelia. To understand the molecular mechanisms that controls multipotency in adult BaSCs, we performed population bulk-RNA-seq and single cell RNA-seq of FACS isolated adult mammary epithelial cells after LC ablation. Upon LC ablation, adult BCs activate a hybrid basal and luminal differentiation program before giving rise to LC, reminiscent of the genetic program that regulate multipotency during embryonic development. Different signaling pathways including Notch, Wnt and Egfr were activated in BaSC and their progeny following LC ablation and blocking these pathways inhibited adult BC multipotency. Altogether, our study demonstrates that heterotypic LC and BC communication is essential to maintain lineage fidelity in glandular epithelial SC during homeostasis and uncovers the lineage trajectory and signaling pathways that promote multipotency during tissue repair.
2020-04-24 | GSE127975 | GEO
Project description:Transdifferentiation of BLaER1 B cell into macrophages is an appropriate model to understand how chromatin behaves along a dynamic process. With this purpose, we have performed chromatin immunoprecipitation experiments of two histone modifications associated to active enhancer activity along 4 time points of BLaER1 transdifferentiation.
2020-05-08 | E-MTAB-9010 | biostudies-arrayexpress
Project description:The mammary gland (MG) is composed of basal cells (BCs) and luminal cells (LCs). While it is generally believed that MG arises from embryonic multipotent progenitors (EMPs), it remains unclear when lineage restriction occurs and what are the mechanisms responsible for the switch from multipotency to unipotency during MG morphogenesis. Here, we performed multicolor lineage tracing and assessed the fate of single embryonic progenitors during mouse MG development. We demonstrated the existence of a developmental switch from multipotency to unipotency during embryonic MG development. Molecular profiling and single cell RNA-seq revealed the hybrid gene expression of EMPs, and the gene trajectory and lineage segregation occurring during MG development. In situ characterization showed that one of the earliest signs of lineage segregation consists in the restricted expression of p63 in the future BCs. Sustained p63 expression during MG development promotes unipotent BC fate in EMPs. Altogether, this study identifies the timing and the mechanisms mediating the switch from multipotency to unipotency during MG development. To understand the molecular mechanisms regulating multipotency during embryonic development, we isolated EMPs by FACS at E14, performed their transcriptional profiling by microarray and compared their transcriptome to adult BCs and LCs
2018-06-01 | GSE99433 | GEO