Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Direct Cell Conversion of Human Fibroblasts to Monocytic phagocytes by Forced Expression of Monocytic Regulatory Network Elements

ABSTRACT: Direct cell conversion is now expected to apply to therapeutic purposes. Although that has been succeeded in several cell types, the mechanism or general way to identify the key transcription factors are still unclear. In addition, most of the cases are not completely identical with the target cells. In previous work, we suggested that cell status is maintained by a homeostatic network of limited number of TFs and no single transcription factor is both necessary and sufficient to drive the differentiation process. Here, identifying the key TFs of human monocyte by combining comparative gene expression analysis and literature based text-mining, we mimicked the monocytic regulatory network in human dermal fibroblasts to induce direct cell conversion of the fibroblasts to monocytes. We suggested that although it is a primary master TF, single TF is not sufficient to induce the direct cell conversion and orchestrated TF regulation is necessary to complete the cell conversion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27304 | GEO | 2011/02/15

SECONDARY ACCESSION(S): PRJNA137123

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Direct Cell Conversion of Human Fibroblasts to Monocytic phagocytes by Forced Expression of Monocytic Regulatory Network Elements

Project description:Direct cell conversion is now expected to apply to therapeutic purposes. Although that has been succeeded in several cell types, the mechanism or general way to identify the key transcription factors are still unclear. In addition, most of the cases are not completely identical with the target cells. In previous work, we suggested that cell status is maintained by a homeostatic network of limited number of TFs and no single transcription factor is both necessary and sufficient to drive the differentiation process. Here, identifying the key TFs of human monocyte by combining comparative gene expression analysis and literature based text-mining, we mimicked the monocytic regulatory network in human dermal fibroblasts to induce direct cell conversion of the fibroblasts to monocytes. We suggested that although it is a primary master TF, single TF is not sufficient to induce the direct cell conversion and orchestrated TF regulation is necessary to complete the cell conversion. Total RNA obtained from human dermal fibroblasts(FIB), human CD14+ monocytes(MON), mock lentivirus vector transduced fibroblasts (FIB-mock), SPI1 transduced fibroblasts (FIB-SPI1), and SPI1, CEBPA, MNDA, IRF8 transduced fibroblasts(FIB-4Fs). The fold change was computed compared with fibroblasts or FIB-mock.

2011-02-15 | E-GEOD-27304 | biostudies-arrayexpress

Transcription factors interfering with dedifferentiation induce direct conversion

Project description:Although transcription factor(TF)s regulate differentiation-related processes, including dedifferentiation and direct conversion, functional interactions between TFs regulating these processes are not well understood. Here we show that TFs preventing dedifferentiation are able to induce direct conversion. Using a neural lineage cell line and a large number of TFs expressed in it, we found a subset of TFs whose overexpression strongly interfered with dedifferentiation triggered by a procedure to induce induced pluripotent stem cells (iPSC), through a maintenance mechanism of the cell-type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, TFs that interfered with dedifferentiation in hepatic lineage cells involved known TFs with induction activity for hepatic lineage cells. Our results suggest that dedifferentiation suppresses a cell-type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types, which may include cancer cells, and might facilitate identification of TFs with induction activity to understand differentiation and tumorigenesis Examination of binding of 3 transcription factors and histone modifications in Neural progenitor like cells.

2013-01-01 | E-GEOD-41252 | biostudies-arrayexpress

Transcription factors interfering with dedifferentiation induce direct conversion

2013-01-01 | GSE41252 | GEO

Single-cell epigenome analysis identifies transcriptional events controlling direct conversion of human fibroblasts to pancreatic ductal-like cells [FI-snMultiome-seq]

Project description:Cell fate can be reprogrammed by ectopic expression of lineage-specific transcription factors (TF). However, the exact cell state transitions during transdifferentiation are still poorly understood. Here, we have generated pancreatic exocrine cells of ductal epithelial identity from human fibroblasts using a set of six TFs. We mapped the molecular determinants of lineage dynamics using a factor-indexing method based on single-nuclei multiome sequencing (FI-snMultiome-seq) that enables dissecting the role of each individual TF and pool of TFs in cell fate conversion. We show that transition from mesenchymal fibroblast identity to epithelial pancreatic exocrine fate involves two deterministic steps: an endodermal progenitor state defined by activation of HHEX with FOXA2 and SOX17, and a temporal GATA4 activation essential for maintenance of pancreatic cell fate program. Collectively, our data suggest that transdifferentiation – although being considered a direct cell fate conversion method – occurs through transient progenitor states orchestrated by stepwise activation of distinct TFs

2023-08-14 | GSE216858 | GEO

Single-cell epigenome analysis identifies transcriptional events controlling direct conversion of human fibroblasts to pancreatic ductal-like cells [ChIP-seq]

2023-08-14 | GSE216857 | GEO

Single-cell epigenome analysis identifies transcriptional events controlling direct conversion of human fibroblasts to pancreatic ductal-like cells [ATAC-seq]

2023-08-14 | GSE216855 | GEO

Single-cell epigenome analysis identifies transcriptional events controlling direct conversion of human fibroblasts to pancreatic ductal-like cells [RNA-seq]

2023-08-14 | GSE216854 | GEO

KLF4 binding is involved in the organization and regulation of 3D enhancer networks during acquisition and maintenance of pluripotency.

Project description:Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors (TFs), as is strikingly exemplified by reprogramming somatic cells to pluripotent stem cells (PSCs) via expression of OCT4, KLF4, SOX2 and cMYC. How TFs orchestrate the complex molecular changes around their target gene loci in a temporal manner remains incompletely understood. Here, using KLF4 as a paradigm, we provide the first TF-centric view of chromatin reorganization and its association to 3D enhancer rewiring and transcriptional changes of linked genes during reprogramming of mouse embryonic fibroblasts (MEFs) to PSCs. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in the connectivity of enhancers, while disruption of individual KLF4 binding sites from PSC-specific enhancers was sufficient to impair enhancer-promoter contacts and reduce expression of associated genes. Our study provides an integrative view of the complex activities of a lineage-specifying TF during a controlled cell fate transition and offers novel insights into the order and nature of molecular events that follow TF binding.

2019-09-03 | PXD014631 | Pride

Rapid chromatin switch in the direct reprogramming of fibroblasts to neurons

Project description:How transcription factors (TFs) reprogram one cell lineage to another remains unclear. Here, we define chromatin accessibility changes induced by the proneural TF Ascl1 throughout conversion of fibroblasts into induced neuronal (iN) cells. Thousands of genomic loci are affected as early as 12 hours after Ascl1 induction. Surprisingly, over 80% of the accessibility changes occur between days 2 and 5 of the 3-week reprogramming process. This chromatin switch coincides with robust activation of endogenous neuronal TFs and nucleosome phasing of neuronal promoters and enhancers. Subsequent morphological and functional maturation of iN cells are accomplished with relatively little chromatin reconfiguration. Integrating chromatin accessibility and transcriptome changes, we built a network model of dynamic TF regulation during iN cell reprogramming, and identified Zfp238, Sox8 and Dlx3 as key TFs downstream of Ascl1. These results reveal a singular, coordinated epigenomic switch during direct reprogramming, in contrast to step-wise cell fate transitions in development.

2017-09-25 | GSE101397 | GEO

Senescence impairs direct conversion of human somatic cells to neurons

Project description:Direct conversion from fibroblasts to neurons is a potential cell replacement therapy for neurological disorders, and a variety of combinations of transcription factors have been tried. We notice that the efficiency of conversion from aging fibroblasts was much lower than in early stage cells, which is consistent with the notion that cellular senescence impairs conversion of fibroblasts to neurons. Here, we found that the transient knockdown of the p16Ink4a/p19Arf locus was sufficient to convert human fibroblasts to neurons. Futhermore, expression of hTERT alone, another mechanism behind immortalization, also induced neuron conversion. Our results show that the acquisition of immortality is a crucial step for the conversion of human fibroblasts into induced neurons.

2012-12-28 | GSE43175 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data