C-Myc alone is enough to reprogram fibroblasts into functional macrophages [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1150966 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30338390_1.fastq.gz | Fastqsanger.gz | |||
| SRR30338390_2.fastq.gz | Fastqsanger.gz | |||
| SRR30338391_1.fastq.gz | Fastqsanger.gz | |||
| SRR30338391_2.fastq.gz | Fastqsanger.gz | |||
| SRR30338392_1.fastq.gz | Fastqsanger.gz |
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Project description:c-Myc alone is enough to reprogram fibroblasts into functional macrophages [scRNA-seq]
| PRJNA1150967 | ENA
Project description:Background Cell therapy based on macrophages is promising in solid tumors, but effective acquisition of macrophages is a challenge. Induced pluripotent stem cell (iPSC)-induced macrophages are a good source but are time-consuming and costly. Macrophages derived from somatic cells by reprogramming technologies have the potential to enable the development of cell-based therapies for numerous malignant diseases. Methods The composition of CD45+ myeloid-like cell complex (MCC) was analyzed by flow cytometry and single-cell sequencing. The engraftment capacity of CD45+ MCC was evaluated by two transplantation assays. Regulation of c-myc on MafB was evaluated by ChIP-qPCR and promoter reporter and dual luciferase assays. The phenotype and phagocytosis of induced macrophages were explored by flow cytometry and immunofluorescence. Leukemia, breast cancer, and patient-derived tumor xenograft models were used to explore the anti-tumor function of induced macrophages. Results Here we report on the establishment of a novel methodology allowing for reprogramming fibroblasts into functional macrophages with phagocytic activity by c-Myc overexpression. Fibroblasts with ectopic expression of c-Myc in iPSC medium rapidly generated CD45+ MCC intermediates with engraftment capacity as well as the repopulation of distinct hematopoietic compartments. MCC intermediates were stably maintained in suspension culture and continuously generated functional and highly pure-induced macrophage (iMac) just by M-CSF cytokine stimulation. Single-cell transcriptomic analysis of MCC intermediates revealed that c-Myc up-regulates the expression of MafB, a major regulator of macrophage differentiation, to promote macrophage differentiation. Characterization of the iMac activity showed NF-κB signaling activation and a pro-inflammatory phenotype. iMac cells display significantly increased in vivo persistence and inhibition of tumor progression in leukemia, breast cancer, and patient-derived tumor xenograft models. Conclusions Our findings demonstrate that c-Myc alone is enough to reprogram fibroblasts into functional macrophages, supporting that c-Myc reprogramming strategy of fibroblasts could help circumvent long-standing obstacles to gaining “off-the-shelf” macrophages for anti-cancer immunotherapy. Keywords c-Myc, fibroblast, macrophage, immunotherapy, reprogramming
2024-09-18 | GSE275457 | GEO
Project description:Background Cell therapy based on macrophages is promising in solid tumors, but effective acquisition of macrophages is a challenge. Induced pluripotent stem cell (iPSC)-induced macrophages are a good source but are time-consuming and costly. Macrophages derived from somatic cells by reprogramming technologies have the potential to enable the development of cell-based therapies for numerous malignant diseases. Methods The composition of CD45+ myeloid-like cell complex (MCC) was analyzed by flow cytometry and single-cell sequencing. The engraftment capacity of CD45+ MCC was evaluated by two transplantation assays. Regulation of c-myc on MafB was evaluated by ChIP-qPCR and promoter reporter and dual luciferase assays. The phenotype and phagocytosis of induced macrophages were explored by flow cytometry and immunofluorescence. Leukemia, breast cancer, and patient-derived tumor xenograft models were used to explore the anti-tumor function of induced macrophages. Results Here we report on the establishment of a novel methodology allowing for reprogramming fibroblasts into functional macrophages with phagocytic activity by c-Myc overexpression. Fibroblasts with ectopic expression of c-Myc in iPSC medium rapidly generated CD45+ MCC intermediates with engraftment capacity as well as the repopulation of distinct hematopoietic compartments. MCC intermediates were stably maintained in suspension culture and continuously generated functional and highly pure-induced macrophage (iMac) just by M-CSF cytokine stimulation. Single-cell transcriptomic analysis of MCC intermediates revealed that c-Myc up-regulates the expression of MafB, a major regulator of macrophage differentiation, to promote macrophage differentiation. Characterization of the iMac activity showed NF-κB signaling activation and a pro-inflammatory phenotype. iMac cells display significantly increased in vivo persistence and inhibition of tumor progression in leukemia, breast cancer, and patient-derived tumor xenograft models. Conclusions Our findings demonstrate that c-Myc alone is enough to reprogram fibroblasts into functional macrophages, supporting that c-Myc reprogramming strategy of fibroblasts could help circumvent long-standing obstacles to gaining “off-the-shelf” macrophages for anti-cancer immunotherapy. Keywords c-Myc, fibroblast, macrophage, immunotherapy, reprogramming
2024-09-18 | GSE275456 | GEO
Project description:Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by Oct4, Sox2, Klf4, plus c-Myc. Recently, Sox2 plus Oct4 were shown to reprogram fibroblasts and Oct4 alone to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here we report that Bmi1 leads to dedifferentiation of mouse fibroblasts into NSC-like cells and, in combination with Oct4, replaces Sox2, Klf4 and c-Myc during reprogramming fibroblasts to iPS cells. Furthermore, activation of sonic hedgehog signalling (by Shh, purmorphamine, or oxysterol) replaces the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One-and two-factor iPS cells are similar to mouse embryonic and adult fibroblasts into iPS cells in global gene expression profile, epigenetic status, in vitro and in bibo differentiation into all three ferm layers, as well as teratoma formation and germline transmission in vivo. These data support that fibroblasts can be reprogrammed into iPS cells by Oct4 alone. Total RNAs were isolated from indicated cells and labeled with Cy3. Hybridization was performed once for each sample.
2010-09-18 | E-GEOD-24208 | biostudies-arrayexpress
Project description:Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by Oct4, Sox2, Klf4, plus c-Myc. Recently, Sox2 plus Oct4 were shown to reprogram fibroblasts and Oct4 alone to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here we report that Bmi1 leads to dedifferentiation of mouse fibroblasts into NSC-like cells and, in combination with Oct4, replaces Sox2, Klf4 and c-Myc during reprogramming fibroblasts to iPS cells. Furthermore, activation of sonic hedgehog signalling (by Shh, purmorphamine, or oxysterol) replaces the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One-and two-factor iPS cells are similar to mouse embryonic and adult fibroblasts into iPS cells in global gene expression profile, epigenetic status, in vitro and in bibo differentiation into all three ferm layers, as well as teratoma formation and germline transmission in vivo. These data support that fibroblasts can be reprogrammed into iPS cells by Oct4 alone.
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Project description:Myc ChIP in HeLa cells and 2091 fibroblasts Keywords: ChIP-chip HeLa cells, quiescent 2091 fibroblasts, and serum stimulated 2091 fibroblasts were used for Myc ChIP reactions.
2008-05-26 | E-GEOD-5197 | biostudies-arrayexpress
Project description:Myc regulates many gene expression during cell growth, development, or other many cellular events. C-Myc is a well known molecule which expression increase in many cancers. Overexpression of c-Myc causes cell transformation, apoptosis, etc. There are several Myc family genes in human, mouse, or other species. The function of N-Myc was well characterized and was similar to that of c-Myc. However, the function of L-Myc is not clearly examined. To examine the function of L-Myc, we perfomed microarray analyses using L-Myc overexpressed human fibroblasts. Adult human fibroblasts were transduced with Myc and their mutants and were used for microarray analyses.
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Project description:Myc regulates many gene expression during cell growth, development, or other many cellular events. C-Myc is a well known molecule which expression increase in many cancers. Overexpression of c-Myc causes cell transformation, apoptosis, etc. There are several Myc family genes in human, mouse, or other species. The function of N-Myc was well characterized and was similar to that of c-Myc. However, the function of L-Myc is not clearly examined. To examine the function of L-Myc, we perfomed microarray analyses using L-Myc overexpressed human fibroblasts.
2010-07-26 | GSE22654 | GEO
Project description:Group 3 medulloblastoma is often associated with MYC amplification or overexpression, while whether MYC overexpression alone is sufficient to induce tumorigenesis is unknown and the cell type(s) which can be transformed by MYC is unclear. Here, by generating a new mouse model, we demonstrated that overexpression of Myc alone is sufficient to transform astrocyte progenitors and granule neuron progenitors (GNP) in the early postnatal cerebellum following orthotopic transplantation. The resulting tumors resemble human Group 3 medulloblastoma in terms of both histology and gene expression profiles. Using these models we found that inhibition of lactate dehydrogenase A (LDHA) significantly reduced both murine and human MYC-driven tumor growth, but did not affect SHH medulloblastoma, indicating that LDHA is potential and specific therapeutic target for MYC-driven medulloblastoma.
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