scholarly journals A mex3 homolog is required for differentiation during planarian stem cell lineage development

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Shu Jun Zhu ◽  
Stephanie E Hallows ◽  
Ko W Currie ◽  
ChangJiang Xu ◽  
Bret J Pearson
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Rna Binding ◽  
Transcriptional Profiling ◽  
Cell Lineage ◽  
Functional Screening ◽  
Differentiated Cells ◽  
Stem Cell Lineage ◽  
A Cell

Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

scholarly journals Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila

PLoS Genetics ◽  
2014 ◽  
Vol 10 (11) ◽  
pp. e1004797 ◽  
Author(s):  
Di Chen ◽  
Chan Wu ◽  
Shaowei Zhao ◽  
Qing Geng ◽  
Yu Gao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Lineage

scholarly journals Biomimetic three-dimensional microenvironment for controlling stem cell fate

2011 ◽  
Vol 1 (5) ◽  
pp. 792-803 ◽  
Author(s):  
Hu Zhang ◽  
Sheng Dai ◽  
Jingxiu Bi ◽  
Kuo-Kang Liu
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Three Dimensional ◽  
Cell Lineage ◽  
Cell Interaction ◽  
Stem Cell Fate ◽  
Cell Microenvironment ◽  
Stem Cell Lineage ◽  
Matrix Cell ◽  
The Individual

Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the individual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.

scholarly journals Bi-directional cell-pericellular matrix interactions direct stem cell fate

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Silvia A. Ferreira ◽  
Meghna S. Motwani ◽  
Peter A. Faull ◽  
Alexis J. Seymour ◽  
Tracy T. L. Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Cell Lineage ◽  
Local Environment ◽  
Pericellular Matrix ◽  
Lineage Specification ◽  
Reciprocal Interactions ◽  
Stem Cell Lineage ◽  
Matrix Interactions ◽  
Insight Into

Abstract Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.

scholarly journals Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mélanie Criqui ◽  
Aditi Qamra ◽  
Tsz Wai Chu ◽  
Monika Sharma ◽  
Julissa Tsao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Chromatin Accessibility ◽  
Telomere Dysfunction ◽  
Epigenetic Alterations ◽  
Dna Hypomethylation ◽  
Murine Embryonic Stem Cell ◽  
Stem Cell Lineage

The precise relationship between epigenetic alterations and telomere dysfunction is still an extant question. Previously, we showed that eroded telomeres lead to differentiation instability in murine embryonic stem cells (mESCs) via DNA hypomethylation at pluripotency-factor promoters. Here, we uncovered that telomerase reverse transcriptase null (Tert-/-) mESCs exhibit genome-wide alterations in chromatin accessibility and gene expression during differentiation. These changes were accompanied by an increase of H3K27me3 globally, an altered chromatin landscape at the Pou5f1/Oct4 promoter, and a refractory response to differentiation cues. Inhibition of the Polycomb Repressive Complex 2 (PRC2), an H3K27 tri-methyltransferase, exacerbated the impairment in differentiation and pluripotency gene repression in Tert-/- mESCs but not wild-type mESCs, whereas inhibition of H3K27me3 demethylation led to a partial rescue of the Tert-/- phenotype. These data reveal a new interdependent relationship between H3K27me3 and telomere integrity in stem cell lineage commitment that may have implications in aging and cancer.

scholarly journals Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies

2020 ◽  
Author(s):  
Cristina Parigini ◽  
Philip Greulich
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Cell Lineage ◽  
Universality Class ◽  
Lineage Tracing ◽  
Self Renewal ◽  
Fundamental Limits ◽  
Challenges And Opportunities

How adult stem cells maintain self-renewing tissues is in vivo commonly assessed by analysing clonal data from cell lineage tracing assays. To identify strategies of stem cell self-renewal requires that different models of stem cell fate choice predict sufficiently different clonal statistics. Here we show that models of cell fate choice can, in homeostatic tissues, be categorized by exactly two ‘universality classes’, whereby models of the same class predict, under asymptotic conditions, the same clonal statistics. Those classes relate to generalizations of the canonical asymmetric vs. symmetric stem cell self-renewal strategies and are differentiated by a conservation law. This poses both challenges and opportunities to identify stem cell self-renewal strategies: while under asymptotic conditions, self-renewal models of the same universality class cannot be distinguished by clonal data only, models of different classes can be distinguished by simple means.

scholarly journals Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cristina Parigini ◽  
Philip Greulich
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Cell Lineage ◽  
Universality Class ◽  
Lineage Tracing ◽  
Self Renewal ◽  
Fundamental Limits ◽  
Challenges And Opportunities

How adult stem cells maintain self-renewing tissues is commonly assessed by analysing clonal data from in vivo cell lineage-tracing assays. To identify strategies of stem cell self-renewal requires that different models of stem cell fate choice predict sufficiently different clonal statistics. Here, we show that models of cell fate choice can, in homeostatic tissues, be categorized by exactly two ‘universality classes’, whereby models of the same class predict, under asymptotic conditions, the same clonal statistics. Those classes relate to generalizations of the canonical asymmetric vs. symmetric stem cell self-renewal strategies and are distinguished by a conservation law. This poses both challenges and opportunities to identify stem cell self-renewal strategies: while under asymptotic conditions, self-renewal models of the same universality class cannot be distinguished by clonal data only, models of different classes can be distinguished by simple means.

Using Single-Cell and Spatial Transcriptomes to Understand Stem Cell Lineage Specification During Early Embryo Development

2020 ◽  
Vol 21 (1) ◽  
pp. 163-181
Author(s):  
Guangdun Peng ◽  
Guizhong Cui ◽  
Jincan Ke ◽  
Naihe Jing
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Fate ◽  
Cell Lineage ◽  
Stem Cell Differentiation ◽  
Early Embryo ◽  
Stem Cell Lineage ◽  
Single Cell Rna Sequencing ◽  
Cell Organization

Embryonic development and stem cell differentiation provide a paradigm to understand the molecular regulation of coordinated cell fate determination and the architecture of tissue patterning. Emerging technologies such as single-cell RNA sequencing and spatial transcriptomics are opening new avenues to dissect cell organization, the divergence of morphological and molecular properties, and lineage allocation. Rapid advances in experimental and computational tools have enabled researchers to make many discoveries and revisit old hypotheses. In this review, we describe the use of single-cell RNA sequencing in studies of molecular trajectories and gene regulation networks for stem cell lineages, while highlighting the integratedexperimental and computational analysis of single-cell and spatial transcriptomes in the molecular annotation of tissue lineages and development during postimplantation gastrulation.

scholarly journals Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Pedro M. Aponte ◽  
Andrés Caicedo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Adult Stem Cells ◽  
Future Research ◽  
Differentiated Cells ◽  
Essential Components ◽  
A Cell ◽  
Cell Niche

Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

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