Capybara: A tool to measure cell identity and fate transitions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA606516 | ENA |
REPOSITORIES: ENA
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Project description:Using our Capybara tool to measure cell identity, we profiled induced endoderm progenitors, reprogrammed from fibroblasts (via overexpression of Hnf4a and Foxa1), and cultured long-term, for 12 months.
2020-02-14 | GSE145251 | GEO
Project description:The embryonic temporal regulator FUSCA3 (FUS3) plays major roles in the establishment of embryonic leaf identity and regulation of developmental timing. Loss-of-function mutations of this B3-domain transcription factor result in replacement of cotyledons with leaves and precocious germination, while constitutive misexpression causes the conversion of leaves into cotyledon-like organs and delays vegetative and reproductive phase transitions. To identify downstream targets of FUS3 involved in vegetative phase transitions, we performed microarray analysis on seedlings that transiently activate FUS3 using the AtML1:FUS3-GR-DEX inducible system. Using this construct, FUS3 is ectopically expressed in the ML1 or epidermal layer and becomes activated upon addition of dexamethasone. We found that activation of FUS3 after germination dampens the expression of genes involved in the biosynthesis and response to the plant hormone ethylene, while a loss-of-function fus3 mutant shows many phenotypes consistent with increased ethylene signaling. This FUS3-dependent regulation of ethylene signaling also impinges on timing functions outside of embryogenesis. Loss of FUS3 function results in accelerated vegetative phase change and this is again partially dependent on functional ethylene action. This alteration in vegetative phase transition is dependent on both embryonic and vegetative FUS3 function, suggesting that this important transcriptional regulator controls both embryonic and vegetative developmental timing. This study indicates that the embryonic regulator FUS3 not only regulates the embryonic-to-vegetative phase transition through hormonal regulation, but also functions postembryonically to modulate vegetative phase transitions by negatively regulating ethylene action.
2011-12-11 | E-MEXP-3465 | biostudies-arrayexpress
Project description:Early mammalian development entails a series of cell fate transitions that includes transit through naïve pluripotency to post-implantation epiblast. This can subsequently give rise to primordial germ cells (PGC), the founding population of the germline lineage. To investigate the gene regulatory networks that control these critical cell fate decisions, we developed a compound-reporter system to track cellular identity in a model of PGC specification (PGC-like cells; PGCLC), and coupled it with unbiased genome-wide CRISPR screening. This enabled identification of key genes both for exit from pluripotency and for acquisition of PGC fate, with further characterisation revealing a central role for the transcription regulators Nr5a2 and Zfp296 in germline ontogeny. Abrogation of these genes results in significantly impaired PGCLC development accompanied with widespread activation (Nr5a2-/-) or inhibition (Zfp296-/-) of WNT pathway components. This leads to aberrant upregulation of the somatic programme or failure to appropriately activate germline genes in PGCLC, respectively, and consequently loss of germ cell identity. Overall our study places Zfp296 and Nr5a2 as key components of an expanded PGC gene regulatory network, and outlines a transferable strategy for identifying critical regulators of complex cell fate transitions.
2018-10-01 | GSE117473 | GEO
Project description:Study hypothesis: This pilot study aims to determine the acceptability (to patients and research nurses), feasibility and validity of a tool to measure patient and primary delays in cancer. In particular this work will:
1. Pilot the recruitment of patients with a recent and established diagnosis of one of seven specific cancers (or groups of cancers) and the administration of the tool by research nurses
2. Assess non-response bias
3. Assess and seek ways to minimize the level of anxiety that may be raised as part of the data collection process
4. Assess completion rates
5. Compare the response to the tool being administered by a research nurse with self-completion facilitated by a research nurse
Primary outcome(s): To compare the two groups in terms of overall completion rates using an intention to treat analysis
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Project description:During cerebral development, a variety of neurons are sequentially generated by self-renewing progenitor cells, apical progenitors (APs). A temporal change in AP identity is thought to produce a diversity of progeny neurons, while underlying mechanisms are largely unknown. Here we performed single cell genome-wide transcriptome profiling of APs at different neurogenic stages, and identified a set of genes that are temporally expressed in APs in a manner independent of differentiation state. Surprisingly, the temporal pattern of such AP gene expression was not affected by arresting cell cycling. Consistently, a transient cell cycle arrest of APs in vivo did not prevent descendant neurons to acquire their correct laminar fates. in vitro cell culture of APs revealed that transitions in AP gene expression involved in both cell-autonomous and non-autonomous mechanisms. These results suggest that timers controlling AP temporal identity run independently of cell cycle progression and Notch activation mode.
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Project description:Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.
2020-12-15 | GSE137708 | GEO
Project description:Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.
2020-12-15 | GSE137707 | GEO
Project description:Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.
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Project description:Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.
2020-12-15 | GSE141269 | GEO
Project description:Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.
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