Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells

Lin, Victor; Zolekar, Ashwini; Shi, Yi; Koneru, Bhuvaneswari; Dimitrijevich, Slobodan D.; Pasqua, Anthony J. Di; Wang, Yu-Chieh

doi:10.1038/s41598-017-05117-2

Cited by 9 publications

(7 citation statements)

References 66 publications

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“…Additionally, our work adds to the molecular mechanisms that have associated membrane potential with stem cells differentation 12,14,[60][61][62] . Of note, previous work has suggested that K + itself may have signaling properties that affect the directed differentiation of hESCs 63 . However, our study indicates that it is V m and not K + itself that is critical.…”

Section: Discussionmentioning

confidence: 98%

Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR

et al. 2022

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Transitioning from pluripotency to differentiated cell fates is fundamental to both embryonic development and adult tissue homeostasis. Improving our understanding of this transition would facilitate our ability to manipulate pluripotent cells into tissues for therapeutic use. Here, we show that membrane voltage (Vm) regulates the exit from pluripotency and the onset of germ layer differentiation in the embryo, a process that affects both gastrulation and left-right patterning. By examining candidate genes of congenital heart disease and heterotaxy, we identify KCNH6, a member of the ether-a-go-go class of potassium channels that hyperpolarizes the Vm and thus limits the activation of voltage gated calcium channels, lowering intracellular calcium. In pluripotent embryonic cells, depletion of kcnh6 leads to membrane depolarization, elevation of intracellular calcium levels, and the maintenance of a pluripotent state at the expense of differentiation into ectodermal and myogenic lineages. Using high-resolution temporal transcriptome analysis, we identify the gene regulatory networks downstream of membrane depolarization and calcium signaling and discover that inhibition of the mTOR pathway transitions the pluripotent cell to a differentiated fate. By manipulating Vm using a suite of tools, we establish a bioelectric pathway that regulates pluripotency in vertebrates, including human embryonic stem cells.

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Section: Discussionmentioning

confidence: 98%

Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR

et al. 2022

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“…Our study was focused on relations between K + transport and stem cell proliferation. Recently, using reflection X-ray fluorescence spectrometry and mass spectrometry, the extensive research of the inorganic components in human stem cells in distinct states of cellular pluripotency was performed 51 . This study revealed that intracellular K + content differs considerably between non-pluripotent and pluripotent cells (hPSCs), and the perturbations of K + homeostasis in the presence of pharmacological drugs affect the intracellular signaling in hPSCs and the cell reprogramming for induced hPSCs production.…”

Section: Discussionmentioning

confidence: 99%

Proliferation-related changes in K+ content in human mesenchymal stem cells

Marakhova

Домнина

Shatrova

et al. 2019

Sci Rep

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Intracellular monovalent ions have been shown to be important for cell proliferation, however, mechanisms through which ions regulate cell proliferation is not well understood. Ion transporters may be implicated in the intracellular signaling: Na+ and Cl− participate in regulation of intracellular pH, transmembrane potential, Ca2+ homeostasis. Recently, it is has been suggested that K+ may be involved in “the pluripotency signaling network”. Our study has been focused on the relations between K+ transport and stem cell proliferation. We compared monovalent cation transport in human mesenchymal stem cells (hMSCs) at different passages and at low and high densities of culture as well as during stress-induced cell cycle arrest and revealed a decline in K+ content per cell protein which was associated with accumulation of G1 cells in population and accompanied cell proliferation slowing. It is suggested that cell K+ may be important for successful cell proliferation as the main intracellular ion that participates in regulation of cell volume during cell cycle progression. It is proposed that cell K+ content as related to cell protein is a physiological marker of stem cell proliferation and may be used as an informative test for assessing the functional status of stem cells in vitro.

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“…This means, that despite the lack of significant concentration differences, K + may be important for initiating cell proliferation as the intracellular ion that participates in regulation of volume and water content. Indeed, iincreasing evidence indicate that K + channels of plasma membrane are involved in regulation of cell proliferation: their expression and function can be regulated by the cell cycle, and inhibition of K + channel activity results in cell cycle arrest 12,26,27,56,57 .…”

Section: Discussionmentioning

confidence: 99%

“…We also found age-dependent decrease in K i per g of cell protein in growing cultures of human mesenchymal stem cells 26 . Of interest, cell K + content assayed by X-ray fluorescence spectrometry and mass spectrometry differs considerably between human pluripotent cells and non-pluripotent cells 27 .…”

Section: Introductionmentioning

confidence: 99%

Intracellular K+ and water content in human blood lymphocytes during transition from quiescence to proliferation

Marakhova

Yurinskaya

Aksenov

et al. 2019

Sci Rep

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Many evidence shows that K+ ions are required for cell proliferation, however, changes in intracellular K+ concentration during transition of cells from quiescence to cycling are insufficiently studied. Here, we show using flame emission assay that a long-term increase in cell K+ content per g cell protein is a mandatory factor for transition of quiescent human peripheral blood lymphocytes (PBL) to proliferation induced by phytohemagglutinin, phorbol ester with ionomycin, and anti-CD3 antibodies with interleukin-2 (IL-2). The long-term increase in K+ content is associated with IL-2-dependent stage of PBL activation and accompanies the growth of small lymphocytes and their transformation into blasts. Inhibition of PBL proliferation with drugs specific for different steps of G0/G1/S transit prevented both blast-transformation and an increase in K+ content per cell protein. Determination of the water content in cells by measuring the density of cells in the Percoll gradient showed that, unlike the K+ content, the concentration of K+ in cell water remains unchanged, since water and K+ change in parallel. Correlation of proliferation with high cell K+ and water content has been confirmed by the data obtained in comparative study of PBL and permanently cycling Jurkat cells. Our data suggest that K+ is important for successful proliferation as the main intracellular ion that participates in regulation of cell water content during cell transition from quiescence to proliferation. We concluded that high K+ content in cells and the associated high water content is a characteristic feature of proliferating cells.

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Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells

Cited by 9 publications

References 66 publications

Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR

Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR

Proliferation-related changes in K+ content in human mesenchymal stem cells

Intracellular K+ and water content in human blood lymphocytes during transition from quiescence to proliferation

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