Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells [RNA-Seq]

ABSTRACT: Exosome, a kind of extracellular vesicles, has been introduced as a vehicle for horizontal transferring of genetic material. We induced autologous exosome containing a cocktail of reprogramming factors (‘reprosome’) to convert fibroblasts into neural progenitor cells (NPC). The fibroblasts were sonicated and subsequently cultured in NSC media for 1 day to induce release of reprosomes composed of reprogramming factors associated to chromatin remodeling and neural lineage-specific factors. After treated with reprosomes, fibroblasts were converted into NPCs (rNPC) with great efficiency via activation of chromatin remodeling, as fast as it required only five days for formation of 1,500 spheroids showing NPC-like phenotype. The rNPCs maintained self-renewal and proliferative properties for several weeks and successfully differentiated into neuron, astrocyte, and oligodendrocyte, in vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and efficient, thus providing a new paradigm for clinical application that requires autologous stem cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98111 | GEO | 2018/04/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells [ncRNA-Seq]

Project description:Exosome, a kind of extracellular vesicles, has been introduced as a vehicle for horizontal transferring of genetic material. We induced autologous exosome containing a cocktail of reprogramming factors (‘reprosome’) to convert fibroblasts into neural progenitor cells (NPC). The fibroblasts were sonicated and subsequently cultured in NSC media for 1 day to induce release of reprosomes composed of reprogramming factors associated to chromatin remodeling and neural lineage-specific factors. After treated with reprosomes, fibroblasts were converted into NPCs (rNPC) with great efficiency via activation of chromatin remodeling, as fast as it required only five days for formation of 1,500 spheroids showing NPC-like phenotype. The rNPCs maintained self-renewal and proliferative properties for several weeks and successfully differentiated into neuron, astrocyte, and oligodendrocyte, in vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and efficient, thus providing a new paradigm for clinical application that requires autologous stem cells.

2018-04-24 | GSE98112 | GEO

Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells [MBD-seq]

2018-04-24 | GSE98110 | GEO

Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells [WTS]

2018-04-24 | GSE98113 | GEO

Genome-wide chromatin binding of Elk1 and Gli2 in chemical induced neural reprogramming

Project description:Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small molecule-driven approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging to develop. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine small molecules (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts towards a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study therefore provides an effective chemical approach for generating neural stem cells from mouse fibroblasts, and reveals mechanistic insights into underlying reprogramming process. Genome-wide binding of Elk1 and Gli2 was analyzed by CHIP-seq for tdMEFs from day 0 (ciNSLC), day 4 (D4), day 8 (D8) of M9-induced neural reprogramming, and ciNSLCs and pri-NPC.

2016-05-15 | E-GEOD-78976 | biostudies-arrayexpress

Genome-wide chromatin landscape of chemical-induced neural stem cell reprogramming from defined fibroblasts

Project description:Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small molecule-driven approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging to develop. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine small molecules (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts towards a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study therefore provides an effective chemical approach for generating neural stem cells from mouse fibroblasts, and reveals mechanistic insights into underlying reprogramming process. Genome-wide epigenetic changes of H3K4me1, H3K4me3, H3K27me3, and H3K27ac were analyzed by CHIP-seq for tdMEFs from day 0 (ciNSLC), day 4 (D4), day 8 (D8) of M9-induced neural reprogramming, and ciNSLCs and pri-NPC.

2016-05-15 | E-GEOD-78977 | biostudies-arrayexpress

Derivation of Neural Stem Cells from human adult peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

Project description:Activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox-2, Oct3/4, C-MyC and Klf-4. The derived NSC could be differentiated to astroglia and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. 11 Human samples from 7 sources representing 4 different cell types: 2 CD34 (CD34+ cells purified from adult peripheral blood), 3 iNS (induced Neural Stem Cells derived directly from CD34+ cells), 2 iNS derived from iPSC (Neural Stem cells differentiated from induced Pluripotent Stem Cells from CD34+ cells), 4 NPC (human primary cultured neural progenitor cells)

2014-01-01 | E-GEOD-44532 | biostudies-arrayexpress

Pluripotent reprogramming arises from a unique subset of pre-disposed human dermal fibroblasts

Project description:Induced cellular reprogramming to the pluripotent state offers a novel stem cell source for autologous transplantation. While recent studies have explored the role of factors required for induced pluripotent stem cell (iPSC) induction, the cellular and molecular basis of reprogramming from human fibroblasts remains elusive. Here, we have identified a subset of human dermal-derived fibroblasts that shares hallmark molecular and epigenetic features with pluripotent cells. Functional studies demonstrate that these cells contribute to the majority of human iPSCs generated from dermal fibroblasts and are dependent on heterogeneous fibroblast microenvironment for reprogramming competency. Molecular characterization indicated these predisposed fibroblasts were unique to other dermal derived stem cells and possessed features of proliferative selfrenewal. Our study reveals human fibroblasts are not equivalently capable of cellular reprogramming, and suggests that reprogramming factors overcome commitment steps that allow predetermined dermal fibroblasts to establish stable pluripotent state.

2021-11-01 | GSE20904 | GEO

Nudt21 controls cell fate by connecting alternative polyadenylation to chromatin signaling

Project description:Cell fate transitions involve rapid changes of gene expression patterns and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we used transcription-factor induced reprogramming of somatic cells into pluripotent cells to screen for novel regulators of cell fate change. We identified the RNA processing factor Nudt21, a component of the pre-mRNA cleavage and polyadenylation complex, as a potent barrier to reprogramming. Importantly, suppression of Nudt21 not only enhanced the generation of induced pluripotent stem cells but also facilitated the conversion of fibroblasts into trophoblast stem cells and delayed the differentiation of myeloid precursor cells into macrophages, suggesting a broader role for Nudt21 in restricting cell fate change. Polyadenylation site sequencing (PAS-seq) revealed that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency. While only a fraction of these transcripts changed expression at the protein level, this fraction was strongly enriched for chromatin regulators, including components of the PAF, polycomb, and trithorax complexes. Co-suppression analysis further suggests that these chromatin factors are largely responsible for Nudt21’s effect on reprogramming, providing a mechanistic basis for our observations. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of mammalian cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.

2018-01-08 | PXD008078 | Pride

Transduction of human fibroblasts with Zic3 combined with OCT4, SOX2 and KLF4 induces stable neural progenitor cell lines

Project description:Lineage specific transcription factors (TF) define and reinforce tissue specific cell types. For instance, stable endoderm progenitors were established from human ESC by constitutive expression of SOX7 or SOX17. We hypothesized that combinatorial expression of OCT4, SOX2 and KLF4M-BM- together with the neural-lineage TF, Zic3, could directly convert fibroblasts into stable neuronal progenitor cells (NPC). Ensuing colonies predominantly expressed genes present in human NPC, as demonstrated by genome wide transcriptional analysis, and this phenotype could be maintained through many passages.M-BM- When injected in immunodeficient mice, Zic3-induced (Zi)NPC form neuroendocrine tumors without evidence of mesoderm or endoderm. In vitro, ZiNPC spontaneously differentiated to neural cells only, and could be differentiated into astrocytes, oligodendrocytes and motor neuron lineages. In conclusion, addition of Zic3 during induced pluripotent stem cell (iPSC) generation, allows for the derivation of stable neural lineage progenitor cells. 3 hESC, 3 hESC-derived neurosphere and 3 ZiNPC samples were analyzed

2012-05-21 | E-GEOD-29770 | biostudies-arrayexpress

Mus musculus

Project description:Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors

| PRJNA143337 | ENA