Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA159475 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In Vivo Organ Regeneration via Stroma-Dependent Adult Lineage Reprogramming
| PRJNA159423 | ENA
Project description:In Vivo Organ Regeneration via Stroma-Dependent Adult Lineage Reprogramming (mRNA)
| PRJNA159473 | ENA
Project description:The liver is a pivotal organ possessing remarkable regenerative capacity. By employing murine liver injury models and lineage tracing strategy, recent studies have demonstrated that differentiated hepatocytes undergo reprogramming to SOX9+HNF4α+ liver progenitor-like cells (LPLCs), and serve as a totally new cell source for mammalian liver regeneration. However, it is largely unknown how hepatocyte reprogramming is regulated. In this study, we focus on analyzing the microenvironment cues in triggering hepatocyte reprogramming in liver injuries. By performing single-cell RNA sequencing (scRNA-seq) of hepatocyte reprogramming in liver injury, we find immune response is significantly activated. Notably, by lineage depletion, macrophages, especially kupffer cells, but not T cells, B cells, natural killer cells or neutrophils, are found essential for hepatocyte reprogramming and liver regeneration. IL-6, derived specifically from activated kupffer cells, triggers hepatocyte reprogramming via gp130/STAT3 signaling. Furthermore, STAT3 triggers gene expression by binding to Arid1a-dependent pre-opened regeneration-responsive enhancers (RREs) of reprogramming genes. Collectively, this study provides key insights into kupffer cells/IL-6/STAT3-mediated hepatocyte reprogramming and liver regeneration, which may serve as the base for new therapeutic strategies in facilitating endogenous repair mechanisms.
2022-08-24 | GSE193849 | GEO
Project description:The liver is a pivotal organ possessing remarkable regenerative capacity. By employing murine liver injury models and lineage tracing strategy, recent studies have demonstrated that differentiated hepatocytes undergo reprogramming to SOX9+HNF4α+ liver progenitor-like cells (LPLCs), and serve as a totally new cell source for mammalian liver regeneration. However, it is largely unknown how hepatocyte reprogramming is regulated. In this study, we focus on analyzing the microenvironment cues in triggering hepatocyte reprogramming in liver injuries. By performing single-cell RNA sequencing (scRNA-seq) of hepatocyte reprogramming in liver injury, we find immune response is significantly activated. Notably, by lineage depletion, macrophages, especially kupffer cells, but not T cells, B cells, natural killer cells or neutrophils, are found essential for hepatocyte reprogramming and liver regeneration. IL-6, derived specifically from activated kupffer cells, triggers hepatocyte reprogramming via gp130/STAT3 signaling. Furthermore, STAT3 triggers gene expression by binding to Arid1a-dependent pre-opened regeneration-responsive enhancers (RREs) of reprogramming genes. Collectively, this study provides key insights into kupffer cells/IL-6/STAT3-mediated hepatocyte reprogramming and liver regeneration, which may serve as the base for new therapeutic strategies in facilitating endogenous repair mechanisms.
2022-08-24 | GSE193848 | GEO
Project description:Remarkable progress has been made in cell fate reprogramming by forced expression of a small number of transcription factors. Major challenges remain, however, in regenerative medicine regarding how to target multiple cell types and direct them to form a functional organ in vivo. Here, we demonstrate that, by changing their stromal microenvironment, adult differentiated cells of endodermal origin can be reprogrammed to generate a functional ectodermal organ. The process of organ regeneration is highly efficient and complete, and depends on epithelial-stromal interactions that lead to successful remodeling of the extracellular matrix and stromal cells that are essential for organ function. Furthermore, it is a multistep process consisting of changes in cell fate, where dedifferentiation occurs more rapidly than redifferentiation, and subsequent morphogenetic reprogramming. Remarkably, neither direct transdifferentiation nor a complete reversion to the pluripotency state is involved in the reprogramming process; instead it features dynamic activities of essential genes that regulate pluripotency and lineage development. Our data have important implications for stem cell biology, cancer biology, and regenerative medicine.
2021-12-31 | GSE37289 | GEO
Project description:Remarkable progress has been made in cell fate reprogramming by forced expression of a small number of transcription factors. Major challenges remain, however, in regenerative medicine regarding how to target multiple cell types and direct them to form a functional organ in vivo. Here, we demonstrate that, by changing their stromal microenvironment, adult differentiated cells of endodermal origin can be reprogrammed to generate a functional ectodermal organ. The process of organ regeneration is highly efficient and complete, and depends on epithelial-stromal interactions that lead to successful remodeling of the extracellular matrix and stromal cells that are essential for organ function. Furthermore, it is a multistep process consisting of changes in cell fate, where dedifferentiation occurs more rapidly than redifferentiation, and subsequent morphogenetic reprogramming. Remarkably, neither direct transdifferentiation nor a complete reversion to the pluripotency state is involved in the reprogramming process; instead it features dynamic activities of essential genes that regulate pluripotency and lineage development. Our data have important implications for stem cell biology, cancer biology, and regenerative medicine.
2021-12-31 | GSE37308 | GEO
Project description:It is widely accepted that adipose-derived regenerative cells (ADRCs) can differentiate into mesodermal lineage cells. However, reprogramming adult ADRCs into mature cardiomyocytes is challenging. We investigated the induction of myocardial differentiation in ADRCs via direct reprogramming using lentiviral gene transfer. We compared gene expression profiling from RNA sequencing of culture ADRCs and embryonic heart organ, and examined candidate transcriptional factors.
2022-06-07 | GSE205165 | GEO
Project description:MicroRNAs (miRNAs) regulate gene expression and generate isoforms (isomiRs) with distinct targeting properties, but their roles in cellular specification and reprogramming remain poorly understood. Here, we investigated miRNAs and isomiRs during direct reprogramming to conventional type 1 dendritic cells (cDC1s), identifying miR-124 and miR-142 as facilitators of the process. The canonical miR-124-3p strand induced a permissive chromatin landscape enriched for cooperative transcription factor motifs, thereby transiently increasing reprogramming efficiency. In contrast, miR-142 enhanced lineage fidelity by repressing fibroblast identity and activating cDC1-specific programs through cooperating isomiRs that drove XCR1 expression and increased type III interferon production. In addition, miR-142 mimics enhanced cancer cell reprogramming and anti-tumor immunity in vivo. Finally, we developed RNA-based cDC1 reprogramming using transcription factor mRNAs combined with miRNA mimics. Together, these findings uncover miRNA isoform diversity as a programmable regulatory layer in immune cell specification and establish RNA-driven reprogramming as a non-viral strategy for cancer immunotherapy.
2026-07-16 | PXD077362 | Pride
Project description:MicroRNAs (miRNAs) regulate gene expression and generate isoforms (isomiRs) with distinct targeting properties, but their roles in cellular specification and reprogramming remain poorly understood. Here, we investigated miRNAs and isomiRs during direct reprogramming to conventional type 1 dendritic cells (cDC1s), identifying miR-124 and miR-142 as facilitators of the process. The canonical miR-124-3p strand induced a permissive chromatin landscape enriched for cooperative transcription factor motifs, thereby transiently increasing reprogramming efficiency. In contrast, miR-142 enhanced lineage fidelity by repressing fibroblast identity and activating cDC1-specific programs through cooperating isomiRs that drove XCR1 expression and increased type III interferon production. In addition, miR-142 mimics enhanced cancer cell reprogramming and anti-tumor immunity in vivo. Finally, we developed RNA-based cDC1 reprogramming using transcription factor mRNAs combined with miRNA mimics. Together, these findings uncover miRNA isoform diversity as a programmable regulatory layer in immune cell specification and establish RNA-driven reprogramming as a non-viral strategy for cancer immunotherapy.
2026-07-16 | PXD058915 | Pride
Project description:Astrocytes in the adult brain show cellular plasticity; however, whether they have the potential to generate multiple lineages remains unclear. Here, we perform in vivo screens and identify DLX2 as a transcription factor that can unleash the multipotentiality of adult resident astrocytes. Genetic lineage tracing and time-course analyses reveal that DLX2 enables astrocytes to rapidly become ASCL1+ neural progenitor cells, which give rise to neurons, astrocytes, and oligodendrocytes in the adult mouse striatum. Single-cell transcriptomics and pseudotime trajectories further confirm a neural stem cell-like behavior of reprogrammed astrocytes, transitioning from quiescence to activation, proliferation, and neurogenesis. Gene regulatory networks and mouse genetics identify and confirm key nodes mediating DLX2-dependent fate reprogramming. These include activation of endogenous DLX family transcription factors and suppression of Notch signaling. Such reprogramming-induced multipotency of resident glial cells may be exploited for neural regeneration.
2022-01-15 | GSE154213 | GEO