Stem Cell Fate: Effect of Hydroxyapatite Nanorods on the Fate of Human Adipose‐Derived Stem Cells Assessed In Situ at the Single Cell Level with a High‐Throughput, Real‐Time Microfluidic Chip (Small 51/2019)

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.

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Wax patterned microwells for stem cell fate study

RSC Advances ◽

10.1039/c6ra22422a ◽

2016 ◽

Vol 6 (106) ◽

pp. 104919-104924 ◽

Cited By ~ 9

Author(s):

Ahmad Z. Qamar ◽

Kshitij Amar ◽

Punit Kohli ◽

Farhan Chowdhury ◽

Mohtashim H. Shamsi

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

High Throughput ◽

Stem Cell Fate

Desktop wax printer was employed to build high throughput platforms for studying stem cells fate.

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Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming

International Journal of Molecular Sciences ◽

10.3390/ijms22115988 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5988

Author(s):

Hyun Kyu Kim ◽

Tae Won Ha ◽

Man Ryul Lee

Keyword(s):

Stem Cells ◽

Single Cell ◽

Cell Fate ◽

Human Cell ◽

Transcriptome Analysis ◽

Single Cell Analysis ◽

Embryonic Stem ◽

Single Cell Level ◽

Cell Analysis ◽

Cell Level

Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.

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Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽

10.1182/blood.2020009778 ◽

2021 ◽

Author(s):

Dirk Loeffler ◽

Florin Schneiter ◽

Weijia Wang ◽

Arne Wehling ◽

Tobias Kull ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Division ◽

Cell Fate ◽

Human Blood ◽

Asymmetric Cell Division ◽

Cell Fates ◽

Hematopoietic Stem ◽

Stem Cell Fate ◽

Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

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

Stem Cells International ◽

10.1155/2018/3256524 ◽

2018 ◽

Vol 2018 ◽

pp. 1-18 ◽

Cited By ~ 16

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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Regulation and Directing Stem Cell Fate by Tissue Engineering Functional Microenvironments: Scaffold Physical and Chemical Cues

Stem Cells International ◽

10.1155/2019/2180925 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 8

Author(s):

Fei Xing ◽

Lang Li ◽

Changchun Zhou ◽

Cheng Long ◽

Lina Wu ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Stem Cell ◽

Growth Factors ◽

Cell Fate ◽

Chemical Cues ◽

Physical Factors ◽

Stem Cell Fate ◽

Physical And Chemical

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

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In situ lineage tracking of human prostatic epithelial stem cell fate reveals a common clonal origin for basal and luminal cells

The Journal of Pathology ◽

10.1002/path.2965 ◽

2011 ◽

Vol 225 (2) ◽

pp. 181-188 ◽

Cited By ~ 51

Author(s):

John K Blackwood ◽

Stuart C Williamson ◽

Laura C Greaves ◽

Laura Wilson ◽

Anastasia C Rigas ◽

...

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Stem Cell Fate ◽

Epithelial Stem Cell ◽

Clonal Origin ◽

Luminal Cells ◽

Lineage Tracking

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Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

Science ◽

10.1126/science.aax1694 ◽

2019 ◽

Vol 366 (6466) ◽

pp. 734-738 ◽

Cited By ~ 11

Author(s):

Antoine de Morree ◽

Julian D. D. Klein ◽

Qiang Gan ◽

Jean Farup ◽

Andoni Urtasun ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Messenger Rna ◽

Adult Stem Cells ◽

Alternative Polyadenylation ◽

Quiescent State ◽

Stem Cell Fate ◽

Activation Rate

Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

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