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Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling

ABSTRACT: Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling

PROVIDER: PRJNA796341 | ENA |

REPOSITORIES: ENA

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Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [scRNA-seq]

Project description:Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [scRNA-seq]

| PRJNA796344 | ENA

Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [RNA-Seq]

Project description:Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [RNA-Seq]

| PRJNA796343 | ENA

Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [RNA-Seq]

Project description:Dendritic cells (DCs) play critical roles in regulating the innate and adaptive immune responses, and have long been a major focus of cancer immunotherapy. Accumulating evidence suggests that conventional type 1 DC (cDC1s) excel in cross-presentation of exogenous antigens on MHC-I molecules, and induction of antitumor CD8+ T cell immunity; however, obtaining large numbers of cDC1s is difficult. The use of reprogramming and differentiation technology is advantageous for obtaining unlimited numbers of autologous cDC1s especially for therapeutic interventions where repeated vaccinations are required. However, generation of cDC1s from human induced pluripotent stem cells (iPSCs) remains elusive.

2022-02-09 | GSE193487 | GEO

Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [scRNA-seq]

2022-02-09 | GSE193485 | GEO

Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-09 | GSE193488 | GEO

Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

Project description:The IRF8-dependent subset of classical dendritic cells (cDC), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor Flt3 ligand (Flt3L) yields very few cDC1 (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) optimize Flt3L-driven development of cDC1 from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1 with the phenotype (CD103+ Dec205+ CD8α+) and expression profile resembling ex vivo cDC1. OP9-DL1-induced cDC1 showed preferential migration towards Ccr7 ligands in vitro and superior T cell cross-priming and antitumor vaccination in vivo. Co-culture with OP9-DL1 also greatly increased the yield of IRF8-dependent CD141+ cDC1 from human bone marrow progenitors cultured with Flt3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1 for functional studies and therapeutic applications.

2018-06-05 | GSE110577 | GEO

Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embyronic and induced pluripotent cells

Project description:Notch signaling regulates several cellular processes including cell fate decisions and proliferation in both invertebrates and mice. However, comparatively less is known about the role of Notch during early human development. Here, we examined the function of Notch signaling during hematopoietic lineage specification from human pluripotent stem cells (hPSCs) of both embryonic and adult fibroblast origin. Using immobilized Notch ligands and siRNA to Notch receptors we have demonstrated that Notch1, but not Notch2 activation, induced HES1 expression and generation of committed hematopoietic progenitors. Using gain and loss of function approaches, this was shown to be attributed to Notch signaling regulation through HES1, that dictated cell fate decisions from bipotent precursors either to the endothelial or hematopoietic lineages at the clonal level. Our study reveals a previously unappreciated role for the Notch pathway during early human hematopoiesis, whereby Notch signaling via HES1 represents a toggle switch of hematopoietic vs. endothelial fate specification. Human pluripotent stem cells (hPSCs) have differentiation potential into three embryonic germ layers including blood. Notch signaling is one of important signaling pathways involved in blood differentiation of hPSCs. Thus, in order to examine the effect of Notch signaling pathways during hematopoietic differentiation of hPSCs, embryoid bodies (EBs) were formed and cultured for 10 days in the combination of cytokines and growth factors (Chadwick, Blood, 2003; 300 ng/ml of SCF, 300 ng/ml of Flt-3L, 10 ng/ml of IL-3, 10 ng/ml of IL-6, and 50 ng/ml of G-CSF) to induce differentiation into blood. Additionally, CD31+CD45- bipotent hemogenic precursors were isolated from day10 hematopoietic EBs (Wang et al., Immunity, 2004)

2013-06-01 | E-GEOD-47466 | biostudies-arrayexpress

Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embyronic and induced pluripotent cells

2013-06-01 | GSE47466 | GEO

Modulation of Notch signaling at early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons.

Project description:Elaboration of protocols for differentiation of human pluripotent stem cells to dopaminergic neurons is an important issue for development of cell replacement therapy for Parkinson’s disease. А number of protocols have been already developed, however, their efficiency and specificity still can be improved. Investigating the role of signaling cascades, important for neurogenesis, can help to solve this problem and to provide a deeper understanding of their role in neuronal development. Notch signaling plays an essential role in development and maintenance of the central nervous system after birth. In our study, we analyzed the effect of Notch activation and inactivation at the early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons. We found, that during first 7 days of differentiation the cells were not sensitive to the Notch inhibition. In contrary, activation of Notch signaling during the same time period led to significant changes and was associated with an increase in expression of genes, specific for caudal parts of the brain, a decrease of expression of genes, specific for forebrain, as well as a decrease of expression of genes, important for the formation of axons and dendrites and microtubule stabilizing proteins.

2023-01-21 | GSE218635 | GEO

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

Project description:This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and to see how well they work in treating patients with advanced or metastatic sarcoma. Vismodegib may slow the growth of tumor cells. Gamma-secretase/notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib together with gamma-secretase/notch signalling pathway inhibitor RO4929097 may be an effective treatment for sarcoma.

| 2091475 | ecrin-mdr-crc

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