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 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.

Lox2, a putative leech segment identity gene, is expressed in the same segmental domain in different stem cell lineages

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 697-710 ◽  
Author(s):  
D. Nardelli-Haefliger ◽  
M. Shankland
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Gene Products ◽  
Cell Lineages ◽  
Stem Cell Lineage ◽  
Hybridization Reaction ◽  
Cell Segment

The segmented tissues of the adult leech arise from a set of five, bilaterally paired embryonic stem cells via a stereotyped sequence of cell lineage. Individual segments exhibit unique patterns of cell differentiation, and previous studies have suggested that each stem cell lineage establishes at least some aspects of its own segmental specificity autonomously. In this paper, we describe a putative leech segment identity gene, Lox2, and examine its expression in the various stem cell lineages. Both sequence analysis and the segmental pattern of Lox2 expression suggest a specific homology to the fruitfly segment identity genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2 RNA over a contiguous domain of 16 midbody segments (M6-M21), including postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts were not detected at the stage when segment identities are first established, suggesting that Lox2 gene products may not be part of the initial specification process. Individual stem cell lineages were labeled by intracellular injection of fluorescent tracers, and single cell colocalization of lineage tracer and hybridization reaction product revealed expression of Lox2 RNA in the progeny of four different stem cells. The segmental domain of Lox2 RNA was very similar in the various stem cell lineages, despite the fact that some stem cells generate one founder cell/segment, whereas other stem cells generate two founder cells/segment.

scholarly journals Control of Embryonic Stem Cell Lineage Commitment by Core Promoter Factor, TAF3

Cell ◽  
2011 ◽  
Vol 146 (5) ◽  
pp. 720-731 ◽  
Author(s):  
Zhe Liu ◽  
Devin R. Scannell ◽  
Michael B. Eisen ◽  
Robert Tjian
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Core Promoter ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Stem Cell Lineage
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