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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216859 | GEO | 2023/08/14

REPOSITORIES: GEO

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

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

2023-08-14 | GSE216858 | GEO

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

Project description:Single-cell epigenome analysis identifies transcriptional events controlling direct conversion of human fibroblasts to pancreatic ductal-like cells

| PRJNA895701 | ENA

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

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

| PRJNA895703 | ENA

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

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

| PRJNA895704 | ENA

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

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

| PRJNA895702 | ENA

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

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

| PRJNA895709 | ENA

Direct conversion of human fibroblasts to dopaminergic neurons.

Project description:Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts. By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.

| S-EPMC3121829 | biostudies-literature

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