scholarly journals Feedback Regulation between Initiation and Maturation Networks Orchestrates the Chromatin Dynamics of Epidermal Lineage Commitment

2018 ◽  
Author(s):  
Lingjie Li ◽  
Yong Wang ◽  
Jessica L. Torkelson ◽  
Gautam Shankar ◽  
Jillian M. Pattison ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Gene ◽  
Regulatory Element ◽  
Feedback Regulation ◽  
Epidermal Differentiation ◽  
Lineage Commitment ◽  
Surface Ectoderm ◽  
Chromatin Dynamics ◽  
Maturation Factor ◽  
Inference Network

SUMMARYTissue development results from lineage-specific transcription factors (TF) programming a dynamic chromatin landscape through progressive cell fate transitions. Here, we interrogate the epigenomic landscape during epidermal differentiation and create an inference network that ranks the coordinate effects of TF-accessible regulatory element-target gene expression triplets on lineage commitment. We discover two critical transition periods: surface ectoderm initiation and keratinocyte maturation, and identify TFAP2C and p63 as lineage initiation and maturation factors, respectively. Surprisingly, we find that TFAP2C, and not p63, is sufficient to initiate surface ectoderm differentiation, with TFAP2C-initiated progenitor cells capable of maturing into functional keratinocytes. Mechanistically, TFAP2C primes the surface ectoderm chromatin landscape and induces p63 expression and binding sites, thus allowing maturation factor p63 to positively auto-regulate its expression and close a subset of the TFAP2C-initiated early program. Our work provides a general framework to infer TF networks controlling chromatin transitions that will facilitate future regenerative medicine advances.

scholarly journals Transcription-factor-mediated epigenetic control of cell fate and lineage commitmentThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 87 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Gary S. Stein ◽  
Sayyed K. Zaidi ◽  
Janet L. Stein ◽  
Jane B. Lian ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Gene ◽  
Peer Review Process ◽  
Regulatory Proteins ◽  
Chromatin Dynamics ◽  
Epigenetic Control ◽  
Regulatory Machinery ◽  
Transcriptional Regulatory ◽  
Proliferation And Differentiation ◽  
Selection Of

Epigenetic control is required to maintain competency for the activation and suppression of genes during cell division. The association between regulatory proteins and target gene loci during mitosis is a parameter of the epigenetic control that sustains the transcriptional regulatory machinery that perpetuates gene-expression signatures in progeny cells. The mitotic retention of phenotypic regulatory factors with cell cycle, cell fate, and tissue-specific genes supports the coordinated control that governs the proliferation and differentiation of cell fate and lineage commitment.

scholarly journals The Yin and Yang of Chromatin Dynamics In Stem Cell Fate Selection

2016 ◽  
Vol 32 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Rene C. Adam ◽  
Elaine Fuchs
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Chromatin Dynamics ◽  
Stem Cell Fate ◽  
Yin And Yang

scholarly journals Transcriptional Regulation of Lineage Commitment - A Stochastic Model of Cell Fate Decisions

2013 ◽  
Vol 9 (8) ◽  
pp. e1003197 ◽  
Author(s):  
Jose Teles ◽  
Cristina Pina ◽  
Patrik Edén ◽  
Mattias Ohlsson ◽  
Tariq Enver ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Stochastic Model ◽  
Cell Fate ◽  
Lineage Commitment ◽  
Cell Fate Decisions

scholarly journals Simple and versatile imaging of genomic loci in live mammalian cells and early pre-implantation embryos using CAS-LiveFISH

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yongtao Geng ◽  
Alexandros Pertsinidis
Keyword(s):  
Mammalian Cells ◽  
Target Gene ◽  
Nuclear Architecture ◽  
Live Cells ◽  
Transcription Activator ◽  
Distal Enhancer ◽  
Chromatin Dynamics ◽  
Guide Rnas ◽  
Early Mouse

AbstractVisualizing the 4D genome in live cells is essential for understanding its regulation. Programmable DNA-binding probes, such as fluorescent clustered regularly interspaced short palindromic repeats (CRISPR) and transcription activator-like effector (TALE) proteins have recently emerged as powerful tools for imaging specific genomic loci in live cells. However, many such systems rely on genetically-encoded components, often requiring multiple constructs that each must be separately optimized, thus limiting their use. Here we develop efficient and versatile systems, based on in vitro transcribed single-guide-RNAs (sgRNAs) and fluorescently-tagged recombinant, catalytically-inactivated Cas9 (dCas9) proteins. Controlled cell delivery of pre-assembled dCas9-sgRNA ribonucleoprotein (RNP) complexes enables robust genomic imaging in live cells and in early mouse embryos. We further demonstrate multiplex tagging of up to 3 genes, tracking detailed movements of chromatin segments and imaging spatial relationships between a distal enhancer and a target gene, with nanometer resolution in live cells. This simple and effective approach should facilitate visualizing chromatin dynamics and nuclear architecture in various living systems.

scholarly journals NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lindsey Seldin ◽  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Spindle Orientation ◽  
Direct Function ◽  
Spindle Positioning ◽  
Adult Mice ◽  
Neonatal Lethality ◽  
The Matrix

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures.

scholarly journals Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity

2020 ◽  
Vol 16 (6) ◽  
pp. 1062-1080
Author(s):  
Jérémie Rispal ◽  
Fabrice Escaffit ◽  
Didier Trouche
Keyword(s):  
Signaling Pathways ◽  
Cell Fate ◽  
Chromatin Modification ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Cell Plasticity ◽  
Chromatin Dynamics ◽  
Irritable Bowel ◽  
The Many

AbstractThe rapid renewal of intestinal epithelium is mediated by a pool of stem cells, located at the bottom of crypts, giving rise to highly proliferative progenitor cells, which in turn differentiate during their migration along the villus. The equilibrium between renewal and differentiation is critical for establishment and maintenance of tissue homeostasis, and is regulated by signaling pathways (Wnt, Notch, Bmp…) and specific transcription factors (TCF4, CDX2…). Such regulation controls intestinal cell identities by modulating the cellular transcriptome. Recently, chromatin modification and dynamics have been identified as major actors linking signaling pathways and transcriptional regulation in the control of intestinal homeostasis. In this review, we synthesize the many facets of chromatin dynamics involved in controlling intestinal cell fate, such as stemness maintenance, progenitor identity, lineage choice and commitment, and terminal differentiation. In addition, we present recent data underlying the fundamental role of chromatin dynamics in intestinal cell plasticity. Indeed, this plasticity, which includes dedifferentiation processes or the response to environmental cues (like microbiota’s presence or food ingestion), is central for the organ’s physiology. Finally, we discuss the role of chromatin dynamics in the appearance and treatment of diseases caused by deficiencies in the aforementioned mechanisms, such as gastrointestinal cancer, inflammatory bowel disease or irritable bowel syndrome.

scholarly journals Chromatin dynamics during hematopoiesis reveal discrete regulatory modules instructing differentiation

2020 ◽  
Author(s):  
Grigorios Georgolopoulos ◽  
Mineo Iwata ◽  
Nikoletta Psatha ◽  
Andrew Nishida ◽  
Tannishtha Som ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Ex Vivo ◽  
Chromatin Accessibility ◽  
Dnase I ◽  
Lineage Commitment ◽  
Gene Promoters ◽  
Chromatin Dynamics ◽  
Regulatory Modules ◽  
Hypersensitive Sites ◽  
Regulatory Landscape

AbstractLineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis illuminates the fine-scale temporal dynamics of these regulatory modules during lineage-resolution between these two fates. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.

scholarly journals The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

2020 ◽  
Author(s):  
Emma Carley ◽  
Rachel K. Stewart ◽  
Abigail Zieman ◽  
Iman Jalilian ◽  
Diane. E. King ◽  
...  
Keyword(s):  
Cell Fate ◽  
Control Cell ◽  
Nuclear Lamina ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Linc Complex ◽  
Force Transmission ◽  
Cell Fate Decisions

AbstractWhile the mechanisms by which chemical signals control cell fate have been well studied, how mechanical inputs impact cell fate decisions are not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells, and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.

scholarly journals Autophagy modulates cell fate decisions during lineage commitment

Autophagy ◽  
2021 ◽  
pp. 1-17
Author(s):  
Kulbhushan Sharma ◽  
Nagham T. Asp ◽  
Sean P. Harrison ◽  
Richard Siller ◽  
Saphira F. Baumgarten ◽  
...  
Keyword(s):  
Cell Fate ◽  
Lineage Commitment ◽  
Cell Fate Decisions

A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signaling

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 115-124
Author(s):  
L. Maves ◽  
G. Schubiger
Keyword(s):  
Cell Fate ◽  
Molecular Basis ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Wing Development ◽  
Downstream Target ◽  
Leg Development ◽  
Disc Cells ◽  
Targeted Expression ◽  
Necessary And Sufficient

We are investigating how Drosophila imaginal disc cells establish and maintain their appendage-specific determined states. We have previously shown that ectopic expression of wingless (wg) induces leg disc cells to activate expression of the wing marker Vestigial (Vg) and transdetermine to wing cells. Here we show that ectopic wg expression non-cell-autonomously induces Vg expression in leg discs and that activated Armadillo, a cytosolic transducer of the Wg signal, cell-autonomously induces Vg expression in leg discs, indicating that this Vg expression is directly activated by Wg signaling. We find that ubiquitous expression of wg in leg discs can induce only dorsal leg disc cells to express Vg and transdetermine to wing. Dorsal leg disc cells normally express high levels of decapentaplegic (dpp) and its downstream target, optomotor-blind (omb). We find that high levels of dpp expression, which are both necessary and sufficient for dorsal leg development, are required for wg-induced transdetermination. We show that dorsalization of ventral leg disc cells, through targeted expression of either dpp or omb, is sufficient to allow wg to induce Vg expression and wing fate. Thus, dpp and omb promote both dorsal leg cell fate as well as transdetermination-competent leg disc cells. Taken together, our results show that the Wg and Dpp signaling pathways cooperate to induce Vg expression and leg-towing transdetermination. We also show that a specific vg regulatory element, the vg boundary enhancer, is required for transdetermination. We propose that an interaction between Wg and Dpp signaling can explain why leg disc cells transdetermine to wing and that our results have implications for normal leg and wing development.

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