scholarly journals Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 70
Author(s):  
Li-Ping Liu ◽  
Dong-Xu Zheng ◽  
Zheng-Fang Xu ◽  
Hu-Cheng Zhou ◽  
Yun-Cong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecules ◽  
Cell Fate ◽  
Early Stage ◽  
Functional Evaluation ◽  
Biological Processes ◽  
Skin Damage ◽  
Skin Substitutes ◽  
Epithelial Stem Cells ◽  
2D And 3D

Amniotic epithelial stem cells (AESCs) are considered as potential alternatives to keratinocytes (KCs) in tissue-engineered skin substitutes used for treating skin damage. However, their clinical application is limited since similarities and distinctions between AESCs and KCs remain unclear. Herein, a transcriptomics analysis and functional evaluation were used to understand the commonalities and differences between AESCs and KCs. RNA-sequencing revealed that AESCs are involved in multiple epidermis-associated biological processes shared by KCs and show more similarity to early stage immature KCs than to adult KCs. However, AESCs were observed to be heterogeneous, and some possessed hybrid mesenchymal and epithelial features distinct from KCs. A functional evaluation revealed that AESCs can phagocytose melanosomes transported by melanocytes in both 2D and 3D co-culture systems similar to KCs, which may help reconstitute pigmented skin. The overexpression of TP63 and activation of NOTCH signaling could promote AESC stemness and improve their differentiation features, respectively, bridging the gap between AESCs and KCs. These changes induced the convergence of AESC cell fate with KCs. In future, modified reprogramming strategies, such as the use of small molecules, may facilitate the further modulation human AESCs for use in skin regeneration.

scholarly journals EBF1 is expressed in pericytes and contributes to pericyte cell commitment

2021 ◽  
Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Cell Lineage ◽  
Cell Maturation ◽  
Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

scholarly journals Transcriptional Regulation of Dental Epithelial Cell Fate

2020 ◽  
Vol 21 (23) ◽  
pp. 8952
Author(s):  
Keigo Yoshizaki ◽  
Satoshi Fukumoto ◽  
Daniel D. Bikle ◽  
Yuko Oda
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Gene Mutations ◽  
Dental Enamel ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Cell Fates ◽  
Chromatin Regulators ◽  
Dental Epithelium ◽  
Potential Tool

Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.

scholarly journals Epigenetic Regulation of Dental Pulp Stem Cell Fate

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Dan Zhou ◽  
Lu Gan ◽  
Yiran Peng ◽  
Yachuan Zhou ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
Dental Pulp ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Stem Cell Fate ◽  
The Past ◽  
Multipotent Differentiation ◽  
Dental Pulp Stem Cell

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

scholarly journals The evolving biology of small molecules: controlling cell fate and identity

2011 ◽  
Vol 366 (1575) ◽  
pp. 2208-2221 ◽  
Author(s):  
Jem A. Efe ◽  
Sheng Ding
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Small Molecules ◽  
Somatic Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Stem Cell Biology ◽  
Vast Number ◽  
Short Period

Small molecules have been playing important roles in elucidating basic biology and treatment of a vast number of diseases for nearly a century, making their use in the field of stem cell biology a comparatively recent phenomenon. Nonetheless, the power of biology-oriented chemical design and synthesis, coupled with significant advances in screening technology, has enabled the discovery of a growing number of small molecules that have improved our understanding of stem cell biology and allowed us to manipulate stem cells in unprecedented ways. This review focuses on recent small molecule studies of (i) the key pathways governing stem cell homeostasis, (ii) the pluripotent stem cell niche, (iii) the directed differentiation of stem cells, (iv) the biology of adult stem cells, and (v) somatic cell reprogramming. In a very short period of time, small molecules have defined a perhaps universally attainable naive ground state of pluripotency, and are facilitating the precise, rapid and efficient differentiation of stem cells into somatic cell populations relevant to the clinic. Finally, following the publication of numerous groundbreaking studies at a pace and consistency unusual for a young field, we are closer than ever to completely eliminating the need for genetic modification in reprogramming.

Targeting Wnt Signaling through Small molecules in Governing Stem Cell Fate and Diseases

2019 ◽  
Vol 19 (3) ◽  
pp. 233-246 ◽  
Author(s):  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Suhanya Veronica Prasad ◽  
Francesco Marotta ◽  
Surajit Pathak
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Small Molecules ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Wnt Pathway ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Stem Cell Fate

Background:The conserved Wnt/β-catenin signaling pathway is responsible for multiple functions including regulation of stem cell pluripotency, cell migration, self-renewability and cell fate determination. This signaling pathway is of utmost importance, owing to its ability to fuel tissue repair and regeneration of stem cell activity in diverse organs. The human adult stem cells including hematopoietic cells, intestinal cells, mammary and mesenchymal cells rely on the manifold effects of Wnt pathway. The consequences of any dysfunction or manipulation in the Wnt genes or Wnt pathway components result in specific developmental defects and may even lead to cancer, as it is often implicated in stem cell control. It is absolutely essential to possess a comprehensive understanding of the inhibition and/ or stimulation of the Wnt signaling pathway which in turn is implicated in determining the fate of the stem cells.Results:In recent years, there has been considerable interest in the studies associated with the implementation of small molecule compounds in key areas of stem cell biology including regeneration differentiation, proliferation. In support of this statement, small molecules have unfolded as imperative tools to selectively activate and inhibit specific developmental signaling pathways involving the less complex mechanism of action. These compounds have been reported to modulate the core molecular mechanisms by which the stem cells regenerate and differentiate.Conclusion:This review aims to provide an overview of the prevalent trends in the small molecules based regulation of stem cell fate via targeting the Wnt signaling pathway.

Limbal melanocytes support limbal epithelial stem cells in 2D and 3D microenvironments

2015 ◽  
Vol 138 ◽  
pp. 70-79 ◽  
Author(s):  
Marc A. Dziasko ◽  
Stephen J. Tuft ◽  
Julie T. Daniels
Keyword(s):  
Stem Cells ◽  
Epithelial Stem Cells ◽  
Limbal Epithelial Stem Cells ◽  
2D And 3D

Dermal papilla-induced hair differentiation of adult epithelial stem cells from human skin

2004 ◽  
Vol 19 (2) ◽  
pp. 207-217 ◽  
Author(s):  
Cecilia Roh ◽  
Qingfeng Tao ◽  
Stephen Lyle
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Cell Fate ◽  
Time Course ◽  
Dermal Papilla ◽  
Fold Increase ◽  
Keratinocyte Differentiation ◽  
Epithelial Stem Cells ◽  
High Calcium ◽  
Keratinocyte Stem Cells

The epithelial-mesenchymal interactions between keratinocyte stem cells and dermal papilla (DP) cells are crucial for normal development of the hair follicle as well as during hair cycling. During the cyclical regrowth of a new lower follicle, the multipotent hair follicle stem cells are stimulated to proliferate and differentiate through interactions with the underlying mesenchymal DP cells. To characterize the events occurring during the process of epithelial stem cell fate determination, we utilized a coculture system by incubating human hair follicle keratinocyte stem cells with DP cells. Using GeneChip microarrays, we analyzed changes in gene expression within the stem cells upon coculture with the DP over a 5-day time course. A number of important signaling pathways and growth factors were regulated. The hair-specific keratin 6hf (K6hf) gene proved a particularly good marker of hair differentiation, with a 7.9-fold increase in mRNA and resulting increased protein levels. The high expression of K6hf was unique to DP-induced keratinocyte differentiation, since expression of K6hf was not induced by high calcium. Since the β-catenin signaling pathway has been implicated in hair follicle development, we examined the role of β-catenin in our system and demonstrated that β-catenin/lef-1 signaling is required for DP-induced hair differentiation.

scholarly journals PASsing on Signals: PAS Kinase (PASK)-mTOR Signaling Conveys Nutrient Sufficiency Signals to Epigenetic (COMPASS) Complexes to Activate Stem Cell Differentiation Program (P15-009-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chintan Kikani ◽  
Michael Xiao ◽  
Xiaoying Wu ◽  
Jared Rutter
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Early Stage ◽  
Stem Cell Differentiation ◽  
Mtor Signaling ◽  
Kinase Assay ◽  
Cell Functions ◽  
Nutrient Signaling

Abstract Objectives To determine how nutrient signaling impacts stem cell functions Methods PASK phosphorylation: We measured in situ phosphorylation of PASK by metabolic 32P labeling of stem cells expressing WT or mutant versions of PASK. PASK Activation: PASK activation was measured using in vitro kinase assay using radio-labeled ATP. Myogenesis: Myogenesis was measured by immunohistological, and immunofluorescent analysis of differentiating muscle stem cells. Antibodies used were: Myogenin (F5D-Developmental Hybridoma), MF20 (Myosin heavy chain), Pax7 and MyoD. Results Stem cell fate in the tissue niche is intimately connected with intracellular metabolic state and the extracellular hormonal stimulations. We have identified PAS domain containing Kinase (PASK) as a stem cell enriched protein kinase that is required for establishment of the differentiation program in many stem cell paradigms. For this function, PASK phosphorylates Wdr5, a member of the COMPASS family of histone methyltransferases, to activate the epigenetic processes required for the stem cell differentiation (eLife, 2016). Here we show that a master nutrient sensor, mTOR complex 1 (mTORC1) activates PASK via multi-site phosphorylation during stem cell differentiation. This phosphorylation of PASK by mTORC1 is required for epigenetic activation of the Myogenin transcription, exit from the self-renewal and induction of the myogenesis program. Our data suggest that mTORC1-PASK signaling generates MyoG + committed myoblasts (epigenetically - an early stage of myogenesis), whereas mTORC1-S6K1 signaling is required for myoblast fusion (translationally - later stage of myogenesis). Conclusions Our discoveries show that nutrient signaling can partition stem cell fates during different stages of the myogenesis program downstream of mTOR signaling via activation of two distinct protein kinases. Funding Sources NIH R01 (Chintan Kikani), HHMI (Jared Rutter) Supporting Tables, Images and/or Graphs

scholarly journals Connexin43 is Dispensable for Early Stage Human Mesenchymal Stem Cell Adipogenic Differentiation But is Protective against Cell Senescence

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 474 ◽  
Author(s):  
Qing Shao ◽  
Jessica L. Esseltine ◽  
Tao Huang ◽  
Nicole Novielli-Kuntz ◽  
Jamie E. Ching ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Junction Protein

In the last couple of decades, there has been a growing optimism surrounding the potential transformative use of human mesenchymal stem cells (MSCs) and human-induced pluripotent stem cells (iPSCs) for regenerative medicine and disease treatment. In order for this to occur, it is first essential to understand the mechanisms underpinning their cell-fate specification, which includes cell signaling via gap junctional intercellular communication. Here, we investigated the role of the prototypical gap junction protein, connexin43 (Cx43), in governing the differentiation of iPSCs into MSCs and MSC differentiation along the adipogenic lineage. We found that control iPSCs, as well as iPSCs derived from oculodentodigital dysplasia patient fibroblasts harboring a GJA1 (Cx43) gene mutation, successfully and efficiently differentiated into LipidTox and perilipin-positive cells, indicating cell differentiation along the adipogenic lineage. Furthermore, the complete CRISPR-Cas9 ablation of Cx43 from iPSCs did not prevent their differentiation into bona fide MSCs or pre-adipocytes, strongly suggesting that even though Cx43 expression is upregulated during adipogenesis, it is expendable. Interestingly, late passage Cx43-ablated MSCs senesced more quickly than control cells, resulting in failure to properly differentiate in vitro. We conclude that despite being upregulated during adipogenesis, Cx43 plays no detectable role in the early stages of human iPSC-derived MSC adipogenic differentiation. However, Cx43 may play a more impactful role in protecting MSCs from premature senescence.

scholarly journals Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF–p53 pathway

2008 ◽  
Vol 183 (7) ◽  
pp. 1243-1257 ◽  
Author(s):  
Motoshi Nagao ◽  
Kenneth Campbell ◽  
Kevin Burns ◽  
Chia-Yi Kuan ◽  
Andreas Trumpp ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Late Stage ◽  
Early Stage ◽  
Dependent Manner ◽  
Self Renewal ◽  
P53 Pathway ◽  
Glial Fate ◽  
Underlying Mechanisms

The modes of proliferation and differentiation of neural stem cells (NSCs) are coordinately controlled during development, but the underlying mechanisms remain largely unknown. In this study, we show that the protooncoprotein Myc and the tumor suppressor p19ARF regulate both NSC self-renewal and their neuronal and glial fate in a developmental stage–dependent manner. Early-stage NSCs have low p19ARF expression and retain a high self-renewal and neurogenic capacity, whereas late-stage NSCs with higher p19ARF expression possess a lower self-renewal capacity and predominantly generate glia. Overexpression of Myc or inactivation of p19ARF reverts the properties of late-stage NSCs to those of early-stage cells. Conversely, inactivation of Myc or forced p19ARF expression attenuates self-renewal and induces precocious gliogenesis through modulation of the responsiveness to gliogenic signals. These actions of p19ARF in NSCs are mainly mediated by p53. We propose that opposing actions of Myc and the p19ARF–p53 pathway have important functions in coordinated developmental control of self-renewal and cell fate choices in NSCs.

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