Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming [ChIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74997 | GEO | 2020/07/22
REPOSITORIES: GEO
Similar Datasets
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
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 | GSE74998 | GEO
Project description:Recent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. poly RNA-Seq was measured before, during and after conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method.
2015-04-30 | E-GEOD-67265 | biostudies-arrayexpress
Project description:During mammalian embryonic development, the primitive streak is initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of handful transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency . Here we show that, during the OSKM-induced reprogramming process toward pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including the mesenchymal to epithelial transition and the activation of late pluripotent markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm. Human differentiated progeny derived from pluripotent stem cells, N=13 Human undifferentiated pluripotent stem cells, N=6 Transgenic ESC line, N=6 Human tissues, N=29 Human tissue-derived cells, N=20 Human nascent reprogrammed cells, N=95 Mouse cells, N=12
2014-04-24 | E-GEOD-50206 | biostudies-arrayexpress
Project description:By somatic cell nuclear transfer, the oocytes can reprogram terminally differentiated cells back to totipotent state. So the oocytes enriched maternal proteins attract great interests in exploring key factors in somatic cell reprogramming. Here, we presented a maternal factor, surfeit locus protein 4 (Surf4), can significantly facilitate the generation of induced pluripotent stem cells (iPSCs) in a proliferation-independent manner. When co-expressed with Oct4, Sox2, Klf4 and c-Myc (OSKM), Surf4 can activate the response to endoplasmic reticulum (ER) stress at early stage of reprogramming. Besides, blocking unfolded protein response (UPR) compromised the effect of Surf4 on reprogramming. In conclusion, Surf4 serves as an activator for somatic cell reprogramming by activating the response to ER stress.
2021-11-18 | GSE176177 | GEO
Project description:Recent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. poly RNA-Seq and Chromatin accesibility (ATAC-seq) were measured during conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method, as well as in mouse emrbyonic fibroblasts, iPSCs and mouse ESCs.
2015-04-30 | E-GEOD-67298 | biostudies-arrayexpress
Project description:Recent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. WGBS (Whole-Genome-Bisulfite-sequencing) were measured during conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method, as well as in mouse emrbyonic fibroblasts, and mouse ESCs.
2015-05-07 | E-GEOD-68601 | biostudies-arrayexpress
Project description:Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Chemicals' acronyms: V, VPA; C, CHIR; 6, 616452; T, tranylcypromine; F, FSK; Z, DZNep; P, PGE2; R, RG108; S, SRT1720; M, 2-Me-5HT; D, D4476; B, Sodium butyrate. To compare the global gene expression pofile of mouse embryonic fibroblasts (MEFs), mouse adult lung fibroblasts (MAFs), mouse neonatal fibroblasts (MNFs), adipose-derived stem cells (ADSCs), chemical induced pluripotent stem cells (CiPS), embryonic stem cells (ESCs) and OSKM-iPSCs. We profiled the mRNA expression of each sample by microarray (Mouse OneArray® v2, Phalanx). Different sample set was normalized for different purpose. Set1: MEFs1, CiPS34, MNF CIPS7, CiPS50 CiPS21, OSKM-iPS1 and ESCs1 were analyzed, each sample have three replicates; Set2: MNFs, MAFs, ADSCs, MNF CiPS1, MAF CiPS3, CiPS45, ADSC CiPS2, OSKM iPS2 and ESCs2 were analyzed, each sample have three replicates; Set3: WT MEFs, ESCs3, CiPS WT1 and CiPS WT2 were analyzed, each sample have two replicates; Set4: MEFs2, SKM-FSK1, SKM-FSK2 and ESCs4 were analyzed, each sample have three replicates; Set5: MEFs3, ESCs5, CiPSCs, D12, D20 and D32 were analyzed, each sample have two replicates.
2013-07-22 | E-GEOD-48201 | biostudies-arrayexpress
Project description:Somatic cells can be directly reprogrammed to pluripotency by exogenous expression of transcription factors, classically Oct4, Sox2, Klf4 and c-Myc. While distinct types of somatic cells can be reprogramed with varying efficiencies and by different modified reprogramming protocols, induced pluripotent stem cell (iPSC) induction remains inefficient and stochastic where a fraction of the cells converts into iPSCs. The nature of rate limiting barrier(s) preventing majority of cells to convert into iPSCs remains elusive. Here we show that neutralizing Mbd3, a core member of the Mbd3/NURD co-repressor and chromatin-remodeling complex, results in deterministic and synchronized reprogramming of multiple differentiated cell types to pluripotency. 100% of Mbd3 depleted mouse and human somatic cells convert into iPSCs after seven days of reprogramming factor induction. Our findings delineate a critical pathway blocking the reestablishment of pluripotency, and offer a novel platform for future dissection of epigenetic dynamics leading to iPSC formation at high resolution. Samples include Mbd3+/+, Mbd3flox/- and Mbd3-/- cells from mouse ES cells and mouse embryonic fibroblast (MEF) before and after DOX induction (initiating reprogramming by OSKM factors).
2013-09-12 | E-GEOD-45352 | biostudies-arrayexpress
Project description:Somatic cells can be directly reprogrammed to pluripotency by exogenous expression of transcription factors, classically Oct4, Sox2, Klf4 and c-Myc. While distinct types of somatic cells can be reprogramed with varying efficiencies and by different modified reprogramming protocols, induced pluripotent stem cell (iPSC) induction remains inefficient and stochastic where a fraction of the cells converts into iPSCs. The nature of rate limiting barrier(s) preventing majority of cells to convert into iPSCs remains elusive. Here we show that neutralizing Mbd3, a core member of the Mbd3/NURD co-repressor and chromatin-remodeling complex, results in deterministic and synchronized reprogramming of multiple differentiated cell types to pluripotency. 100% of Mbd3 depleted mouse and human somatic cells convert into iPSCs after seven days of reprogramming factor induction. Our findings delineate a critical pathway blocking the reestablishment of pluripotency, and offer a novel platform for future dissection of epigenetic dynamics leading to iPSC formation at high resolution. Samples include Mbd3+/+, Mbd3flox/- and Mbd3-/- cells from mouse ES cells and mouse embryonic fibroblast (MEF) before and after DOX induction (initiating reprogramming by OSKM factors). Two histone modifications are given: H3K4me3, H3K27me3. In addition binding data of Mbd3 and Mi2B in various stages.
2013-09-12 | E-GEOD-49766 | biostudies-arrayexpress