Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA168028 | ENA |
REPOSITORIES: ENA
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Project description:Recent studies showed that Induced pluripotent stem cells (iPSCs) could hold memory of their origin and exhibit skewed differentiation potential. This finding reveals a severe limit for the application of iPSCs in cell-based therapy in case certain cell types are not available for reprograming from patients. Here we show that under a typical condition for mammary differentiation, iPSCs derived from mouse mammary epithelium cells (ME-iPSCs) exhibit mammary signature gene expression and chromatin epigenetic modification, leading to smooth progress for mammary gland formation. In contrast, iPSCs reprogramed from tail fibroblasts (TF-iPSCs) displayed fibroblast specific signature that is not compatible for mammary differentiation both in vitro and in vivo. Strikingly, when co-culturing with ME-iPSCs or under pregnant condition, the fibroblast specific signature of TF-iPSCs was erased and the cells gained enhanced ability for mammary differentiation. These findings provide new insights into the precise control of differentiation conditions for future personalized cell-based therapy. Microarray analysis of three cell types with three biological replications.
2015-05-28 | E-GEOD-38471 | biostudies-arrayexpress
Project description:Recent studies showed that Induced pluripotent stem cells (iPSCs) could hold memory of their origin and exhibit skewed differentiation potential. This finding reveals a severe limit for the application of iPSCs in cell-based therapy in case certain cell types are not available for reprograming from patients. Here we show that under a typical condition for mammary differentiation, iPSCs derived from mouse mammary epithelium cells (ME-iPSCs) exhibit mammary signature gene expression and chromatin epigenetic modification, leading to smooth progress for mammary gland formation. In contrast, iPSCs reprogramed from tail fibroblasts (TF-iPSCs) displayed fibroblast specific signature that is not compatible for mammary differentiation both in vitro and in vivo. Strikingly, when co-culturing with ME-iPSCs or under pregnant condition, the fibroblast specific signature of TF-iPSCs was erased and the cells gained enhanced ability for mammary differentiation. These findings provide new insights into the precise control of differentiation conditions for future personalized cell-based therapy.
2015-05-28 | GSE38471 | GEO
Project description:The integration of cell metabolism with signalling pathways, transcription factor networks and epigenetic mediators is critical in coordinating molecular and cellular events during embryogenesis. Induced pluripotent stem cells (IPSCs) are an established model for embryogenesis, germ layer specification and cell lineage differentiation, advancing the study of human embryonic development and the translation of innovations in drug discovery, disease modelling and cell-based therapies. The metabolic regulation of IPSC pluripotency is mediated by balancing glycolysis and oxidative phosphorylation, but there is a paucity of data regarding the influence of individual metabolite changes during cell lineage differentiation. We used <sup>1</sup>H NMR metabolite fingerprinting and footprinting to monitor metabolite levels as IPSCs are directed in a three-stage protocol through primitive streak/mesendoderm, mesoderm and chondrogenic populations. Metabolite changes were associated with central metabolism, with aerobic glycolysis predominant in IPSC, elevated oxidative phosphorylation during differentiation and fatty acid oxidation and ketone body use in chondrogenic cells. Metabolites were also implicated in the epigenetic regulation of pluripotency, cell signalling and biosynthetic pathways. Our results show that <sup>1</sup>H NMR metabolomics is an effective tool for monitoring metabolite changes during the differentiation of pluripotent cells with implications on optimising media and environmental parameters for the study of embryogenesis and translational applications.
2023-05-24 | MTBLS4854 | MetaboLights
Project description:Rank signaling regulates mammary gland development and epithelial cell differentiation. Rank receptor is expressed by mammary basal and luminal populations, but, unlike luminal Rank, the contribution of basal Rank signaling to MG homeostasis remains poorly studied. We have combined timely regulated basal specific Rank expression with lineage tracing models and unveiled that basal Rank signaling controls basal cell identity in postnatal mammary glands. Ectopic basal Rank disrupts basal but also luminal cell identity, resulting in aberrant luminal-like differentiation of basal cells and impaired lactogenesis. Mechanistically, overactivation of basal Rank signaling leads to basal cell lineage infidelity, illustrated by the appearance of premalignant lesions composed by a basal-derived hybrid population with alveolar features which ultimately generates basal and luminal breast adenocarcinomas. Proteomic, transcriptomic and chromatin analyses support that the loss of tumor suppressive epigenetic regulators driven by basal Rank contributes to epithelial cell dedifferentiation and tumorigenesis. The basal Rank signature generated associates to poor prognosis particularly in human adenocarcinomas of the luminal subtype stressing the clinical relevance of our findings. Interestingly, our results reinforce the idea that luminal breast tumors might originate from basal cells that have suffered a luminal-like aberrant dedifferentiation triggered by Rank signaling.
2026-02-02 | PXD054102 | Pride
Project description:Rank signaling regulates mammary gland development and epithelial cell differentiation. Rank receptor is expressed by mammary basal and luminal populations, but unlike that of luminal, the contribution of basal Rank signaling to mammary gland homeostasis remains poorly studied. Combining timely-regulated, basal-specific Rank expression with lineage tracing strategies we unveiled that Rank signaling controls basal cell identity in postnatal mammary glands. Enhanced basal Rank disrupts basal and luminal cell identity, resulting in aberrant luminal-like differentiation of basal cells, defective lactation and the appearance of premalignant lesions composed of a basal-derived hybrid population with luminal/alveolar features, which ultimately generates basal and luminal breast adenocarcinomas. Mechanistically, phospho-proteomic, transcriptomic and chromatin analyses support that basal Rank activation triggers the loss of tumor suppressive epigenetic regulators, leading to chromatin remodeling, disruption of basal identity and tumorigenesis. We uncover a basal Rank gene signature that can be predictive of progression from in situ to invasive adenocarcinomas and associates with poor prognosis in breast cancer patients, particularly in those diagnosed with luminal adenocarcinomas, underlining the clinical relevance of our findings. Our results reinforce the idea that basal lineage infidelity triggered by Rank signaling contribute to generation from pre-invasive lesions and transition to invasive breast cancer.
2026-02-02 | PXD058134 | Pride
Project description:Differentiation of stem cells embedded within the mammary epithelium is orchestrated by lineage-specifying transcription factors. Unlike the well-defined luminal hierarchy, dissection of the basal lineage has been hindered by a lack of specific markers. Inhibitor of Differentiation 4 (ID4) is a basally-restricted helix-loop-helix (HLH) transcription factor essential for mammary development. Here we show that ID4 is highly expressed in basal stem cells and decreases during myoepithelial differentiation. By integrating transcriptomic, proteomic and chromatin-association data we reveal that ID4 is required to suppress myoepithelial gene expression and cell fate.
2021-01-25 | PXD017517 | Pride
Project description:To understand induction of cornification genes during lineage appropriate (keratinocyte differentiation) and inappropriate (fibroblast senescence) conditions , we generated histone modification and gene expression datasets. Then we compared keratinocyte's datasets with fibroblast senescence ones in this study.
2021-10-23 | GSE180361 | GEO
Project description:To understand induction of cornification genes during lineage appropriate (keratinocyte differentiation) and inappropriate (fibroblast senescence) conditions , we generated histone modification and gene expression datasets. Then we compared keratinocyte's datasets with fibroblast senescence ones in this study.
2021-10-23 | GSE180358 | GEO
Project description:To understand induction of cornification genes on lineage appropriate (keratinocyte differentiation) and inappropriate (fibroblast senescence) conditions , we generated histone modification and gene expression dataset. Then we compared these keratinocyte's dataset with our previous fibroblast senescence dataset in the study.
2021-01-04 | GSE130457 | GEO
Project description:Epigenetic memory in induced pluripotent stem cells (iPSCs), with regards to their somatic cell type of origin, might lead to variations in their differentiation capacities. In this context, iPSCs from human CD34+ hematopoietic stem cells (HSCs) might be more suitable for hematopoietic differentiation than commonly used fibroblast-derived iPSCs. To investigate the influence of an epigenetic memory on the ex vivo expansion of iPSCs into erythroid cells, we compared iPSCs from human neural stem cells (NSCs) and human cord blood-derived CD34+ HSCs and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells (RBCs). Although genome-wide DNA methylation profiling at all promoter regions demonstrates an epigenetic memory of iPSCs with regards to their somatic cell type of origin, we found a similar hematopoietic induction potential and erythroid differentiation pattern. All human iPSC lines showed terminal maturation into normoblasts and enucleated RBCs, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the CD34+ HSC-derived iPSCs. More detailed methylation analysis of the hematopoietic and erythrocyte promoters identified similar CpG methylation levels in the CD34+ iPSCs and NSC iPSCs, which confirms their comparable erythroid differentiation potential.
2015-02-20 | GSE55109 | GEO