Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generation of induced progenitor-like cells from mature epithelial cells using interrupted reprogramming

ABSTRACT: A suitable source of progenitor cells is required to attenuate disease or affect cure. We present a novel interrupted reprogramming strategy to generate induced Progenitor-Like (iPL) cells using carefully timed -expression of induced Pluripotent Stem cell reprogramming factors (Oct4, Sox2, Klf4 and c-Myc; OSKM) from non-proliferative Club cells. Interrupted reprogramming allowed controlled expansion yet preservation of lineage commitment. Under clonogenic conditions, iPL cells expanded and functioned as a bronchiolar progenitor-like population to generate mature Club cells, mucin-producing goblet cells, and CFTR-expressing ciliated epithelium. In vivo, iPL cells can repopulate CFTR-deficient epithelium. This interrupted reprogramming process could be metronomically applied, to achieve controlled progenitor-like proliferation. By carefully controlling the duration of -expression of OSKM, iPL cells don't become pluripotent and maintain their memory of origin and retain their ability to efficiently return to their original phenotype. A generic technique to produce highly specified populations may have significant implications for regenerative medicine. Microarray analysis of genome-wide transcriptional changes showed Club-iPL cells have minimal expression of ES cell-related genes (e.g. Nanog, Utf1, Dapp4) and maintained significant overlapping expression of Club cell-related genes. Further analysis showed that the expression of large numbers of genes temporally changed during Dox-driven expansion of Club cells but returned upon withdrawal of the factors.

ORGANISM(S): Mus musculus

PROVIDER: GSE105775 | GEO | 2017/10/24

SECONDARY ACCESSION(S): PRJNA415379

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Interrupted reprogramming of Alveolar Type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis

Project description:We describe here an interrupted reprogramming strategy to generate "induced Progenitor-Like (iPL) cells" from Alveolar Epithelial Type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc; OSKM) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state. Microarray analysis of genome-wide transcriptional changes showed the ability of AEC-II-iPL cells to return to the original phenotype

2018-09-26 | GSE115247 | GEO

Generation of induced progenitor-like cells from mature epithelial cells using interrupted reprogramming

Project description:Generation of induced progenitor-like cells from mature epithelial cells using interrupted reprogramming

| PRJNA415379 | ENA

Interrupted reprogramming of Alveolar Type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis

Project description:Interrupted reprogramming of Alveolar Type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis

| PRJNA474235 | ENA

Interrupted reprogramming into induced pluripotent stem cells does not rejuvenate human mesenchymal stromal cells

Project description:Interrupted reprogramming into induced pluripotent stem cells does not rejuvenate human mesenchymal stromal cells

| PRJNA475735 | ENA

OSKM induce extraembryonic endoderm stem (iXEN) cells in parallel to iPS cells

Project description:While the reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, they also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established alongside the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. Several studies have shown that endodermal genes are upregulated in fibroblasts undergoing reprogramming, although whether endodermal genes promote or inhibit acquisition of pluripotency is unclear. We show that, in fibroblasts undergoing conventional reprogramming, OSKM-induced expression of endodermal genes leads to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to iPS cells, indicating that OSKM are sufficient to drive cells to two distinct fates during reprogramming. Sequence-based mRNA transcriptional profiling of three different cell lines (MEF, XEN, iXEN) with multiple biological replicates, under two different growth medium conditions (ESC medium, XEN medium) for XEN and iXEN cells.

2016-03-03 | E-GEOD-77550 | biostudies-arrayexpress

OSKM induce extraembryonic endoderm stem (iXEN) cells in parallel to iPS cells

2016-03-03 | GSE77550 | GEO

A revised airway epithelial hierarchy includes CFTR-expressing ionocytes

Project description:Airways conduct gases to the lung and are disease sites of asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells by proximodistal location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. We developed 'pulse-seq' , combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that characterize cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease.

2018-07-30 | GSE103354 | GEO

Human transcription factors responsive to initial reprogramming are predominantly legitimate during iPSC reprogramming

Project description:The four transcription factors OCT4, SOX2, KLF4 and MYC (OSKM) together can convert human fibroblasts to induced pluripotent stem cells (iPSCs). It is, however, perplexing that they can do so only for a rare population of the starting cells with a long latency. Transcription factors (TFs) define identities of both the starting fibroblasts and the end product, iPSCs, and are of paramount importance for the reprogramming process as well. It is critical to upregulate or activate iPSC-enriched TFs while downregulate or silence the fibroblast-enriched TFs. This report explores the initial TF responses to OSKM as the molecular underpinnings for both the potency aspect and limitation sides of the OSKM reprogramming. The author first defined the TF reprogramome, i.e., the full complement of TFs to be reprogrammed. Most TFs were resistant to OSKM reprogramming at the initial stages, which agrees with the inefficiency and long latency of iPSC reprogramming. Surprisingly, the current analyses revealed that the majority of the TFs (83 genes) that did respond to OSKM induction underwent legitimate reprogramming. The initial legitimate transcriptional responses of TFs to OSKM reprogramming were observed from fibroblasts from a different individual. Such early biased legitimate reprogramming of the responsive TFs aligns well with the robustness aspect of the otherwise inefficient and stochastic OSKM reprogramming

2020-12-08 | GSE159410 | GEO

Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming [ATAC-Seq]

Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.

2020-07-22 | GSE149500 | GEO

Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming [RNA-Seq]

2020-07-22 | GSE74998 | GEO