scholarly journals m6A is required for resolving progenitor identity during planarian stem cell differentiation

2021 ◽  
Author(s):  
Yael Dagan ◽  
Yarden Yesharim ◽  
Ashley R. Bonneau ◽  
Schraga Schwartz ◽  
Peter W. Reddien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Differentiation ◽  
Histone Variants ◽  
Cell Lineages ◽  
Base Modification ◽  
Undifferentiated Cells ◽  
Chromatin Modifying Complex ◽  
Transcriptional State

Regeneration requires accurate production of missing cell lineages. Cell production is driven by changes to gene expression, which is shaped by multiple layers of regulation. Here, we find that the ubiquitous mRNA base-modification, m6A, is required for proper cell fate choice and cellular maturation in planarian stem cells (neoblasts). We mapped m6A-enriched regions in 7,600 planarian genes, and found that perturbation of the m6A pathway resulted in progressive deterioration of tissues and death. Using single cell RNA sequencing of >20,000 cells following perturbation of the pathway, we discovered that m6A negatively regulates transcription of histone variants, and that inhibition of the pathway resulted in accumulation of undifferentiated cells throughout the animal in an abnormal transcriptional state. Analysis of >1000 planarian gene expression datasets revealed that the inhibition of the chromatin modifying complex NuRD had almost indistinguishable consequences, unraveling an unappreciated link between m6A and chromatin modifications. Our findings reveal that m6A is critical for planarian stem cell homeostasis and gene regulation in regeneration.

scholarly journals Multi-omic profiling of histone variant H3.3 lysine 27 methylation reveals a distinct role from canonical H3 in stem cell differentiation

2022 ◽  
Author(s):  
Yekaterina Kori ◽  
Peder J. Lund ◽  
Matteo Trovato ◽  
Simone Sidoli ◽  
Zuofei Yuan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Histone Variants ◽  
Chromatin Accessibility ◽  
Histone Variant ◽  
Post Translational Modifications ◽  
Histone H3.3 ◽  
Distinct Role

Histone variants, such as histone H3.3, replace canonical histones within the nucleosome to alter chromatin accessibility and gene expression. Although the biological roles of selected histone post-translational modifications (PTMs) have...

scholarly journals Advances in Chromodomain Helicase DNA-Binding (CHD) Proteins Regulating Stem Cell Differentiation and Human Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Caojie Liu ◽  
Ning Kang ◽  
Yuchen Guo ◽  
Ping Gong
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Dna Binding ◽  
Cell Fate ◽  
Developmental Disorders ◽  
Regulation Of Gene Expression ◽  
Stem Cell Differentiation ◽  
Human Diseases ◽  
Health Maintenance

Background: Regulation of gene expression is critical for stem cell differentiation, tissue development, and human health maintenance. Recently, epigenetic modifications of histone and chromatin remodeling have been verified as key controllers of gene expression and human diseases.Objective: In this study, we review the role of chromodomain helicase DNA-binding (CHD) proteins in stem cell differentiation, cell fate decision, and several known human developmental disorders and cancers.Conclusion: CHD proteins play a crucial role in stem cell differentiation and human diseases.

scholarly journals Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation

2019 ◽  
Author(s):  
Jesse R Raab ◽  
Deepthi Y Tulasi ◽  
Kortney E Wager ◽  
Jeremy M Morowitz ◽  
Scott T Magness ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Differentiation ◽  
Chromatin Accessibility ◽  
Intestinal Stem Cell ◽  
Open Chromatin ◽  
Chromatin Dynamics ◽  
Quantitative Classification ◽  
Specific Manner

ABSTRACTIntestinal stem cell (ISC) plasticity is thought to be regulated by broadly-permissive chromatin shared between ISCs and their progeny. Here, we utilize a Sox9EGFP reporter to examine chromatin across ISC differentiation. We find that open chromatin regions (OCRs) can be defined as broadly-permissive or dynamic in a locus-specific manner, with dynamic OCRs found primarily in loci consistent with distal enhancers. By integrating gene expression with chromatin accessibility at transcription factor (TF) motifs in context of Sox9EGFP populations, we classify broadly-permissive and dynamic chromatin relative to TF usage. These analyses identify known and potential regulators of ISC differentiation via their association with dynamic changes in chromatin. We observe ISC expansion in Id3-null mice, consistent with computational predictions. Finally, we examine the relationship between gene expression and 5-hydroxymethylcytosine (5hmC) in Sox9EGFP populations, which reveals 5hmC enrichment in absorptive lineage specific genes. Our data demonstrate that intestinal chromatin dynamics can be quantitatively defined in a locus-specific manner, identify novel potential regulators of ISC differentiation, and provide a chromatin roadmap for further dissecting the role of cis regulation of cell fate in the intestine.

Concentration-dependent gene expression responses to flusilazole in embryonic stem cell differentiation cultures

2011 ◽  
Vol 251 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Dorien A.M. van Dartel ◽  
Jeroen L.A. Pennings ◽  
Liset J.J. de la Fonteyne ◽  
Karen J.J. Brauers ◽  
Sandra Claessen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation

ming is expressed in neuroblast sublineages and regulates gene expression in the Drosophila central nervous system

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 943-952 ◽  
Author(s):  
X. Cui ◽  
C.Q. Doe
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Fate ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cell Lineage ◽  
Cell Lineages ◽  
Finger Protein ◽  
Cell Diversity

Cell diversity in the Drosophila central nervous system (CNS) is primarily generated by the invariant lineage of neural precursors called neuroblasts. We used an enhancer trap screen to identify the ming gene, which is transiently expressed in a subset of neuroblasts at reproducible points in their cell lineage (i.e. in neuroblast ‘sublineages’), suggesting that neuroblast identity can be altered during its cell lineage. ming encodes a predicted zinc finger protein and loss of ming function results in precise alterations in CNS gene expression, defects in axonogenesis and embryonic lethality. We propose that ming controls cell fate within neuroblast cell lineages.

scholarly journals Polyamine-controlled proliferation and protein biosynthesis are independent determinants of hair follicle stem cell fate

2020 ◽  
Author(s):  
Kira Allmeroth ◽  
Christine S. Kim ◽  
Andrea Annibal ◽  
Andromachi Pouikli ◽  
Carlos Andrés Chacón-Martínez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Cell Fate ◽  
Protein Biosynthesis ◽  
Mrna Translation ◽  
Stem Cell Differentiation ◽  
List Type ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Hair Follicle Stem Cell

AbstractStem cell differentiation is accompanied by an increase in mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine, and spermine that are essential for cell growth and stem cell maintenance. However, the role of polyamines as endogenous effectors of stem cell fate and whether they act through translational control remains obscure. Here, we investigated the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. HFSCs showed lower translation rates than progenitor cells, and a forced suppression of translation by direct targeting of the ribosome or through specific depletion of natural polyamines elevated stemness. In addition, we identified N1-acetylspermidine as a novel parallel regulator of cell fate decisions, increasing proliferation without reducing translation. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions.Key PointsLow mRNA translation rates characterize hair follicle stem cell (HFSC) stateDepletion of natural polyamines enriches HFSCs via reduced translationN1-acetylspermidine promotes HFSC state without reducing translationN1-acetylspermidine expands the stem cell pool through elevated proliferation

scholarly journals Regulatory network characterization in development: challenges and opportunities

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1477
Author(s):  
Guangdun Peng ◽  
Jing-Dong J. Han
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Mammalian Development ◽  
Distinct Cell ◽  
Challenges And Opportunities ◽  
Cell Processes ◽  
Early Mammalian Development

Embryonic development and stem cell differentiation, during which coordinated cell fate specification takes place in a spatial and temporal context, serve as a paradigm for studying the orderly assembly of gene regulatory networks (GRNs) and the fundamental mechanism of GRNs in driving lineage determination. However, knowledge of reliable GRN annotation for dynamic development regulation, particularly for unveiling the complex temporal and spatial architecture of tissue stem cells, remains inadequate. With the advent of single-cell RNA sequencing technology, elucidating GRNs in development and stem cell processes poses both new challenges and unprecedented opportunities. This review takes a snapshot of some of this work and its implication in the regulative nature of early mammalian development and specification of the distinct cell types during embryogenesis.

scholarly journals N6-Methyladenosine in RNA and DNA: An Epitranscriptomic and Epigenetic Player Implicated in Determination of Stem Cell Fate

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Pengfei Ji ◽  
Xia Wang ◽  
Nina Xie ◽  
Yujing Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Direct Interaction ◽  
Limited Information ◽  
Stem Cell Fate ◽  
Base Modification ◽  
Dna And Rna ◽  
Proliferation And Differentiation

Vast emerging evidences are linking the base modifications and determination of stem cell fate such as proliferation and differentiation. Among the base modification markers extensively studied, 5-methylcytosine (5-mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as important epigenetic markers involved in regulation of cellular biological processes. N6-Methyladenosine modification in DNA (m6dA), mRNA (m6A), tRNA, and other noncoding RNAs has been defined as another important epigenetic and epitranscriptomic marker in eukaryotes in recent years. The mRNA m6A modification has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (m6A writer), demethylases (m6A eraser), and direct interaction proteins (readers), while limited information on the DNA m6dA is available. The levels and the landscapes of m6A in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the lifespan. Additionally, progress has been made in appreciation of the link between aberrant m6A modification in stem cells and diseases, like cancers and neurodegenerative disorders. These achievements are inspiring scientists to further uncover the epigenetic mechanisms for stem cell development and to dissect pathogenesis of the multiple diseases conferred by development aberration of the stem cells. This review article will highlight the research advances in the role of m6A methylation modifications of DNA and RNA in the regulation of stem cell and genesis of the closely related disorders. Additionally, this article will also address the research directions in the future.

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