scholarly journals Using single-cell entropy to describe the dynamics of reprogramming and differentiation of induced pluripotent stem cells

2020 ◽  
Vol 34 (30) ◽  
pp. 2050288
Author(s):  
Y. Ye ◽  
Z. Yang ◽  
M. Zhu ◽  
J. Lei
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Cell Level ◽  
Macroscopic Variable ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) provide a great model to study the process of stem cell reprogramming and differentiation. Single-cell RNA sequencing (scRNA-seq) enables us to investigate the reprogramming process at single-cell level. Here, we introduce single-cell entropy (scEntropy) as a macroscopic variable to quantify the cellular transcriptome from scRNA-seq data during reprogramming and differentiation of iPSCs. scEntropy measures the relative order parameter of genomic transcriptions at single cell level during the process of cell fate changes, which show increase tendency during differentiation, and decrease upon reprogramming. Hence, scEntropy provides an intrinsic measurement of the cell state, and can be served as a pseudo-time of the stem cell differentiation process. Moreover, based on the evolutionary dynamics of scEntropy, we construct a phenomenological Fokker-Planck equation model and the corresponding stochastic differential equation for the process of cell state transitions during pluripotent stem cell differentiation. These equations provide further insights to infer the processes of cell fates changes and stem cell differentiation. This study is the first to introduce the novel concept of scEntropy to quantify the biological process of iPSC, and suggests that the scEntropy can provide a suitable macroscopic variable for single cells to describe cell fate transition during differentiation and reprogramming of stem cells.

scholarly journals Using single-cell entropy to describe the dynamics of reprogramming and differentiation of induced pluripotent stem cells

2020 ◽  
Author(s):  
Yusong Ye ◽  
Zhuoqin Yang ◽  
Meixia Zhu ◽  
Jinzhi Lei
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Cell Level ◽  
Macroscopic Variable ◽  
Induced Pluripotent

AbstractInduced pluripotent stem cells (iPSCs) provide a great model to study the process of stem cell reprogramming and differentiation. Single-cell RNA sequencing (scRNA-seq) enables us to investigate the reprogramming process at single-cell level. Here, we introduce single-cell entropy (scEntropy) as a macroscopic variable to quantify the cellular transcriptome from scRNA-seq data during reprogramming and differentiation of iPSCs. scEntropy measures the relative order parameter of genomic transcriptions at single cell level during the process of cell fate changes, which show increase tendency during differentiation, and decrease upon reprogramming. Hence, scEntropy provides an intrinsic measurement of the cell state, and can be served as a pseudo-time of the stem cell differentiation process. Moreover, based on the evolutionary dynamics of scEntropy, we construct a phenomenological Fokker-Planck equation model and the corresponding stochastic differential equation for the process of cell state transitions during pluripotent stem cell differentiation. These equations provide further insights to infer the processes of cell fates changes and stem cell differentiation. This study is the first to introduce the novel concept of scEntropy to quantify the biological process of iPSC, and suggests that the scEntropy can provide a suitable macroscopic variable for single cells to describe cell fate transition during differentiation and reprogramming of stem cells.

scholarly journals Conducting Polymer Mediated Electrical Stimulation Induces Multilineage Differentiation with Robust Neuronal Fate Determination of Human Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 658 ◽  
Author(s):  
Eva Tomaskovic-Crook ◽  
Qi Gu ◽  
Siti N Abdul Rahim ◽  
Gordon G Wallace ◽  
Jeremy M Crook
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Electrical Stimulation ◽  
Cell Differentiation ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Chemical Inducers ◽  
Neuronal Fate ◽  
Induced Pluripotent

Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) to augment biocompatibility and cell-effects. Extending our earlier work, which showed that CP-mediated electrical stimulation promotes human neural stem cell differentiation, here we report using electroactive PPy containing the anionic dopant dodecylbenzenesulfonate (DBS) to modulate the fate determination of human induced pluripotent stem cells (iPSCs). Remarkably, the stimulation without conventional chemical inducers resulted in the iPSCs differentiating to cells of the three germ lineages—endoderm, ectoderm, and mesoderm. The unstimulated iPSC controls remained undifferentiated. Phenotypic characterisation further showed a robust induction to neuronal fate with electrical stimulation, again without customary chemical inducers. Our findings add to the growing body of evidence supporting the use of electrical stimulation to augment stem cell differentiation, more specifically, pluripotent stem cell differentiation, and especially neuronal induction. Moreover, we have shown the versatility of electroactive PPy as a cell-compatible platform for advanced stem cell research and translation, including identifying novel mechanisms of fate regulation, tissue development, electroceuticals, and regenerative medicine.

scholarly journals Plant stem-cell organization and differentiation at single-cell resolution

2020 ◽  
Vol 117 (52) ◽  
pp. 33689-33699
Author(s):  
James W. Satterlee ◽  
Josh Strable ◽  
Michael J. Scanlon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Cell Function ◽  
Ectopic Expression ◽  
Cellular Level ◽  
Organizing Center ◽  
Cell Niche

Plants maintain populations of pluripotent stem cells in shoot apical meristems (SAMs), which continuously produce new aboveground organs. We used single-cell RNA sequencing (scRNA-seq) to achieve an unbiased characterization of the transcriptional landscape of the maize shoot stem-cell niche and its differentiating cellular descendants. Stem cells housed in the SAM tip are engaged in genome integrity maintenance and exhibit a low rate of cell division, consistent with their contributions to germline and somatic cell fates. Surprisingly, we find no evidence for a canonical stem-cell organizing center subtending these cells. In addition, trajectory inference was used to trace the gene expression changes that accompany cell differentiation, revealing that ectopic expression of KNOTTED1 (KN1) accelerates cell differentiation and promotes development of the sheathing maize leaf base. These single-cell transcriptomic analyses of the shoot apex yield insight into the processes of stem-cell function and cell-fate acquisition in the maize seedling and provide a valuable scaffold on which to better dissect the genetic control of plant shoot morphogenesis at the cellular level.

scholarly journals Topography induced stiffness alteration of stem cells influences osteogenic differentiation

2020 ◽  
Vol 8 (9) ◽  
pp. 2638-2652 ◽  
Author(s):  
Liangliang Yang ◽  
Qi Gao ◽  
Lu Ge ◽  
Qihui Zhou ◽  
Eliza M. Warszawik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Osteogenic Differentiation ◽  
Single Cell ◽  
Cell Morphology ◽  
Stem Cell Differentiation ◽  
Cell Stiffness ◽  
Biological Processes

Topography-driven alterations to single cell stiffness rather than alterations in cell morphology, is the underlying driver for influencing cell biological processes, particularly stem cell differentiation.

scholarly journals Ultra-multiplexed analysis of single-cell dynamics reveals logic rules in differentiation

2019 ◽  
Vol 5 (4) ◽  
pp. eaav7959 ◽  
Author(s):  
Ce Zhang ◽  
Hsiung-Lin Tu ◽  
Gengjie Jia ◽  
Tanzila Mukhtar ◽  
Verdon Taylor ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Cell Fate Decisions ◽  
Cellular Microenvironments

Dynamical control of cellular microenvironments is highly desirable to study complex processes such as stem cell differentiation and immune signaling. We present an ultra-multiplexed microfluidic system for high-throughput single-cell analysis in precisely defined dynamic signaling environments. Our system delivers combinatorial and time-varying signals to 1500 independently programmable culture chambers in week-long live-cell experiments by performing nearly 106 pipetting steps, where single cells, two-dimensional (2D) populations, or 3D neurospheres are chemically stimulated and tracked. Using our system and statistical analysis, we investigated the signaling landscape of neural stem cell differentiation and discovered “cellular logic rules” that revealed the critical role of signal timing and sequence in cell fate decisions. We find synergistic and antagonistic signal interactions and show that differentiation pathways are highly redundant. Our system allows dissection of hidden aspects of cellular dynamics and enables accelerated biological discovery.

scholarly journals Definitive Endoderm Formation from Plucked Human Hair-Derived Induced Pluripotent Stem Cells and SK Channel Regulation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Anett Illing ◽  
Marianne Stockmann ◽  
Narasimha Swamy Telugu ◽  
Leonhard Linta ◽  
Ronan Russell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Human Hair ◽  
Definitive Endoderm ◽  
Sk Channel ◽  
Induced Pluripotent

Pluripotent stem cells present an extraordinary powerful tool to investigate embryonic development in humans. Essentially, they provide a unique platform for dissecting the distinct mechanisms underlying pluripotency and subsequent lineage commitment. Modest information currently exists about the expression and the role of ion channels during human embryogenesis, organ development, and cell fate determination. Of note, small and intermediate conductance, calcium-activated potassium channels have been reported to modify stem cell behaviour and differentiation. These channels are broadly expressed throughout human tissues and are involved in various cellular processes, such as the after-hyperpolarization in excitable cells, and also in differentiation processes. To this end, human induced pluripotent stem cells (hiPSCs) generated from plucked human hair keratinocytes have been exploitedin vitroto recapitulate endoderm formation and, concomitantly, used to map the expression of the SK channel (SKCa) subtypes over time. Thus, we report the successful generation of definitive endoderm from hiPSCs of ectodermal origin using a highly reproducible and robust differentiation system. Furthermore, we provide the first evidence that SKCas subtypes are dynamically regulated in the transition from a pluripotent stem cell to a more lineage restricted, endodermal progeny.

scholarly journals Enhanced Osteogenic Differentiation of Pluripotent Stem Cells via γ-Secretase Inhibition

2021 ◽  
Vol 22 (10) ◽  
pp. 5215
Author(s):  
Summer Helmi ◽  
Leili Rohani ◽  
Ahmed Zaher ◽  
Youssry El Hawary ◽  
Derrick Rancourt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Notch Signaling ◽  
Induced Pluripotent Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Healing ◽  
Pluripotent Stem Cells ◽  
Healing Process ◽  
Stem Cell Differentiation ◽  
Induced Pluripotent

Bone healing is a complex, well-organized process. Multiple factors regulate this process, including growth factors, hormones, cytokines, mechanical stimulation, and aging. One of the most important signaling pathways that affect bone healing is the Notch signaling pathway. It has a significant role in controlling the differentiation of bone mesenchymal stem cells and forming new bone. Interventions to enhance the healing of critical-sized bone defects are of great importance, and stem cell transplantations are eminent candidates for treating such defects. Understanding how Notch signaling impacts pluripotent stem cell differentiation can significantly enhance osteogenesis and improve the overall healing process upon transplantation. In Rancourt’s lab, mouse embryonic stem cells (ESC) have been successfully differentiated to the osteogenic cell lineage. This study investigates the role of Notch signaling inhibition in the osteogenic differentiation of mouse embryonic and induced pluripotent stem cells (iPS). Our data showed that Notch inhibition greatly enhanced the differentiation of both mouse embryonic and induced pluripotent stem cells.

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 HIF-1α Affects the Neural Stem Cell Differentiation of Human Induced Pluripotent Stem Cells via MFN2-Mediated Wnt/β-Catenin Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Peng Cui ◽  
Ping Zhang ◽  
Lin Yuan ◽  
Li Wang ◽  
Xin Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Neural Stem Cell ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Induced Pluripotent

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.

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