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The circadian regulator PER1 promotes cell reprogramming by inhibiting inflammatory signaling from macrophages

ABSTRACT: Fibroblasts can be reprogrammed to induced neurons (iNs) via transducion of Ascl1, Brn2, and Myt1l. To understand the roles of the circadian regulators Per1 and Per2 on the reprogramming, embryonic fibroblasts from wild type (WT), Per1-/-, and Per2-/- mice were transduced with the three genes and cells were harvested for scRNA-seq on days 4, 7, and 10 after transduction.

ORGANISM(S): Mus musculus

PROVIDER: GSE227621 | GEO | 2023/11/09

REPOSITORIES: GEO

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The circadian regulator PER1 promotes cell reprogramming by inhibiting inflammatory signaling from macrophages

Project description:Fibroblasts can be reprogrammed to induced neurons (iNs) via transducion of Brn2, Ascl1, and Myt1l (BAM). To understand the roles of the circadain regulators Per1 and Per2 on the reprogramming, embryonic fibroblasts from wild type (WT), Per1-/-, and Per2-/- mice were transduced with the three genes and the cells were harvested on day 0, 2, and 4 after transduction for RNA-seq.

2023-11-09 | GSE227140 | GEO

Hierarchical mechanisms for transcription factor-mediated reprogramming of fibroblasts to neurons

Project description:Here we reveal a hierarchical mechanism in the direct conversion of fibroblasts into induced neuronal (iN) cells mediated by the transcription factors Ascl1, Brn2, and Myt1l.

2013-10-24 | GSE43916 | GEO

Hierarchical mechanisms for transcription factor-mediated reprogramming of fibroblasts to neurons

Project description:Here we reveal a hierarchical mechanism in the direct conversion of fibroblasts into induced neuronal (iN) cells mediated by the transcription factors Ascl1, Brn2, and Myt1l. Examination of global transcriptional changes and mapping genome-wide transcription factors occupancy at distinct time points during the transdifferentiation process

2013-04-10 | E-GEOD-43916 | biostudies-arrayexpress

Core Circadian Clock Genes Per1 and Per2 regulate the Rhythm in Photoreceptor Outer Segment Phagocytosis [RPE]

Project description:Retinal photoreceptors undergo daily renewal of their distal outer segments, a process indispensable for maintaining retinal health. Photoreceptor Outer Segment (POS) phagocytosis occurs as a daily peak, roughly about one hour after light onset. However, the underlying cellular and molecular mechanisms which initiate this process are still unknown. Here we show that, under constant darkness, mice deficient for core circadian clock genes (Per1 and Per2), lack a daily peak in POS phagocytosis. By qPCR analysis we found that core clock genes were rhythmic over 24h in both WT and Per1, Per2 double mutant whole retinas. More precise transcriptomics analysis of laser capture microdissected WT photoreceptors revealed no differentially expressed genes between time-points preceding and during the peak of POS phagocytosis. By contrast, we found that microdissected WT retinal pigment epithelium (RPE) had a number of genes that were differentially expressed at the peak phagocytic time-point compared to adjacent ones. We also found a number of differentially expressed genes in Per1, Per2 double mutant RPE compared to WT ones at the peak phagocytic time-point. Finally, based on STRING analysis we found a group of interacting genes which potentially drive POS phagocytosis in the RPE. This potential pathway consists of genes such as: Pacsin1, Syp, Camk2b and Camk2d among others. Our findings indicate that Per1 and Per2 are necessary clock components for driving POS phagocytosis and suggest that this process is transcriptionally driven by the RPE.

2021-06-01 | GSE172438 | GEO

Core Circadian Clock Genes Per1 and Per2 regulate the Rhythm in Photoreceptor Outer Segment Phagocytosis [Photoreceptor]

2021-06-01 | GSE172437 | GEO

KMT2B is selectively required for neuronal transdifferentiation [ChIP-seq]

Project description:Transdifferentiation of fibroblasts into induced Neuronal cells (iNs) by neuronal-specific transcription factors Brn2, Myt1l and Ascl1 is a paradigmatic example of inter-lineage conversion across epigenetically distant cells. Despite tremendous progress on the transcriptional hierarchy underlying transdifferentiation, the enablers of the concomitant epigenome resetting remain to be elucidated. Here we investigated the role of KMT2A and KMT2B, two histone H3 lysine 4 methylases with cardinal roles in development, through individual and combined inactivation. We found that Kmt2b, whose human homologue’s mutations cause dystonia, is selectively required for iN conversion through the suppression of the alternative myocyte program and the induction of neuronal maturation genes.

2018-09-29 | GSE120635 | GEO

KMT2B is selectively required for neuronal transdifferentiation [RNAseq]

2018-09-26 | GSE120440 | GEO

Direct lineage conversion of terminally differentiated hepatocytes to functional neurons

Project description:Mouse fibroblasts and hepatocyte can be directly reprogrammed to induced neuronal (iN) cells. Genome-wide expression analysis showed that Hep-iN cells had not only induced a neuronal transcriptional program but also effectively silenced the hepatocyte transcriptome suggesting that the reprogramming factors lead to a binary lineage switch decision rather than an induction of hybrid phenotypes. Similarly, the fibroblast-specific transcriptional program was downregulated in fibroblast-derived iN cells. BAM = infection with the 3 factors (Ascl1 - Brn2 - Myt1l) . ATT = Hepatocytes_derived_induced_neurons derived from TauGFP-AlbCre-R26-lsl-tomato Total RNA obtained from MEFs subjected to 21 days lentivirus infection for neuronal induction compared to uninfected MEFs.

2011-08-30 | E-GEOD-30102 | biostudies-arrayexpress

Direct lineage conversion of terminally differentiated hepatocytes to functional neurons

2011-08-31 | GSE30102 | GEO

Circadian proteome atlas of wild-type and Per1-/-/Per2-/- mice models across eight organs

Project description:a circadian proteome atlas of eight organs, namely suprachiasmatic nucleus (SCN), hypothalamus (HPOA), liver (LIV), gall bladder (GBD), brown adipose tissue (BAT), kidney (KDN), heart (HEA) and muscle (MUS), from wild-type (WT) and Per1-/-/Per2-/- (DKO) mice housed under constant darkness and ad libitum feeding, collected every two hours for deep proteomic analysis over two days

2023-11-28 | PXD047352 |

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