Generation of induced progenitor-like cells from mature epithelial cells using interrupted reprogramming
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PROVIDER: PRJNA415379 | ENA |
REPOSITORIES: ENA
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Project description: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.
2017-10-24 | GSE105775 | GEO
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
Project description:Interrupted reprogramming of Alveolar Type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis
| PRJNA474235 | ENA
Project description:A suitable source of progenitor cells is required to attenuate disease or affect cure. We present an "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 cystic fibrosis transmembrane conductance regulator (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 do not become pluripotent, and they 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.
| S-EPMC5785620 | biostudies-literature
Project description:Chemical induction of liver progenitor cells from mature hepatocytes
| PRJNA347361 | ENA
Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Exiqon miRCURY microarrays. This was compared to profiles from mature human hepatocytes. Foetal LPCs exhibit a distinct miRNA profile consistent with a stem cell signature, cell division, and some liver-specific functions. 3 independent samples of second trimester liver progenitor cells were prolfiled along with 3 independent mature hepatocyte samples.
2015-05-01 | E-GEOD-57833 | biostudies-arrayexpress
Project description:Mechanistic studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPC) through to mature naïve T cells. We developed a serum free, artificial thymic organoid (ATO) system that supports highly efficient and reproducible in vitro differentiation and positive selection to generate conventional human T cells from all sources of HSPCs. Deep-sequencing of the TCR variable genes was performed to compare the diversity of the TCR repertoire between ATO-derived CD8SP T cells and naive CD8SP T cells from thymus and blood.
2017-02-17 | GSE94968 | GEO
Project description:Transcriptome differences between mature luminal and luminal progenitor cells of the breast
| PRJNA886710 | ENA
Project description:Currently, much effort is directed to the development of new cell sources for clinical therapy using cell fate conversion approaches by small molecules. Direct lineage reprogramming to a progenitor state has been reported in terminally differentiated rodent hepatocytes, yet remains a challenge in human hepatocytes. Human hepatocytes were isolated from healthy and diseased donor livers and reprogrammed into progenitor cells by two small molecules, A83-01 and CHIR99021 (AC), in the presence of EGF and HGF. The stemness properties of human chemically derived hepatic progenitors (hCdHs) were tested by standard in vitro and in vivo assays and transcriptome profiling. We developed a robust culture system for generating hCdHs with therapeutic potential. The use of HGF proved to be an essential determinant of fate conversion process. Based on functional evidence, activation of HGF/MET signal transduction system collaborated with A83-01 and CHIR99021 to allow a rapid expansion of progenitor cells through activation of ERK pathway. hCdHs expressed hepatic progenitor marker genes and proteins, and could self-renew for at least 10 passages while retaining normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. RNASeq gene expression profiling confirmed transcriptional reprogramming of hCdHs toward a progenitor state and suppression of mature hepatocyte transcripts. Upon intrasplenic transplantation into immunocompromised mice with acute liver injury, hCdHs effectively repopulated damaged parenchyma. Our study is a first report of successful reprogramming of human hepatocytes to a population of proliferating bipotent cells with regenerative potential. hCdHs may provide a nove tool that permits expansion and genetic manipulation of patient-specific progenitors to study regeneration and repair of diseased liver.
2019-05-08 | GSE114643 | GEO
Project description:It has been demonstrated that cardiac progenitor cells (CPCs) represent a more effective cell-based therapy for treatment of myocardial infarction. Unfortunately, their therapeutic application is limited by low yield of cell harvesting, declining quality and quantity during the ageing process, and the need for highly invasive heart biopsy. Therefore, there is an emerging interest in generating CPC-like stem cells from somatic cells via somatic reprogramming. This novel approach would provide an unlimited source of stem cells with cardiac differentiation potential. Here we would firstly discuss the different types of CPC and their importance in stem cell therapy for treatment of myocardial infarction; secondly, the necessity of generating induced CPC from somatic cells via somatic reprogramming; and finally the current progress of somatic reprogramming in cardiac cells, especially induced CPC generation.
| S-EPMC5438743 | biostudies-literature