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Evolution, Maintenance and Molecular/Cellular Mechanisms of Totipotency, Pluripotency and Cell Stemness

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 5363

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Guest Editor
Transplant Immunology, The Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: macrophages; actin cytoskeleton; RhoA pathway; chronic rejection; transplantation; germ cells; stem cells; Xenopus laevis; development
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Special Issue Information

Dear Colleagues,

Cell stemness is the ability for self renewal (immortality) and differentiation into specialized cells. The self renewal/differentation is achieved through asymmetric cell division, which creates offsprings of different fates: one retaining stemness and another differentiating into a specialized cell. Depending on developmental potential, stem cells can be totipotent, pluripotent, or unipotent. Any adult organism has tissue- and organ-specific stem cells necessary for homeostasis and regeneration. Besides naturally occurring stem cells, there are also artificially created stem cells reprogrammed in vitro into the state of pluripotency. Although the whole embryonic development is based on the programmed and tightly regulated switch from the state of stemness and totipotency to the state of differentiation and specialization, and stem cells are also widely used in regenerative medicine, very little is known about the molecules and signaling pathways regulating stemness, asymmetric divisions, self-renewal, and switch between stemness and differentiation. Even less is known about how stemness evolved. For this special issue, we invite original research and review manuscripts which cover molecular and cellular mechanisms of stemness and its evolution.

Prof. Dr. Malgorzata Kloc
Guest Editor

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Keywords

  • stemness
  • totipotent
  • self-renewal
  • asymmetric division

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Published Papers (3 papers)

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Research

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17 pages, 7212 KiB  
Article
The Gap Junction Inhibitor Octanol Decreases Proliferation and Increases Glial Differentiation of Postnatal Neural Progenitor Cells
by Rocío Talaverón, Camilo J. Morado-Díaz, Alejandro Herrera, Victoria Gálvez, Angel M. Pastor and Esperanza R. Matarredona
Int. J. Mol. Sci. 2024, 25(12), 6288; https://doi.org/10.3390/ijms25126288 - 7 Jun 2024
Viewed by 812
Abstract
Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. [...] Read more.
Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. In this work we aimed to evaluate the effect of the blockade of gap junctional communication on proliferation and cell fate of NPCs obtained from the SVZ of postnatal rats. NPCs were isolated and expanded in culture as neurospheres. Electron microscopy revealed the existence of gap junctions among neurosphere cells. Treatment of cultures with octanol, a broad-spectrum gap junction blocker, or with Gap27, a specific blocker for gap junctions formed by connexin43, produced a significant decrease in bromodeoxyuridine incorporation. Octanol treatment also exerted a dose-dependent antiproliferative effect on glioblastoma cells. To analyze possible actions on NPC fate, cells were seeded in the absence of mitogens. Treatment with octanol led to an increase in the percentage of astrocytes and oligodendrocyte precursors, whereas the percentage of neurons remained unchanged. Gap27 treatment, in contrast, did not modify the differentiation pattern of SVZ NPCs. Our results indicate that general blockade of gap junctions with octanol induces significant effects on the behavior of postnatal SVZ NPCs, by reducing proliferation and promoting glial differentiation. Full article
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12 pages, 2445 KiB  
Article
Regulatory Elements Outside Established Pou5f1 Gene Boundaries Are Required for Multilineage Differentiation of Embryonic Stem Cells
by Veronika V. Ermakova, Nikita P. Fokin, Nikolay D. Aksenov, Evgeny I. Bakhmet, Ekaterina V. Aleksandrova, Andrey A. Kuzmin and Alexey N. Tomilin
Int. J. Mol. Sci. 2023, 24(20), 15434; https://doi.org/10.3390/ijms242015434 - 21 Oct 2023
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Abstract
The transcription factor Oct4 can rightfully be considered a pivotal element in maintaining pluripotency. In addition, its ability to function as a pioneer factor enables the reprogramming of somatic cells back into a pluripotent state. To better understand the regulation of the Oct4-encoding [...] Read more.
The transcription factor Oct4 can rightfully be considered a pivotal element in maintaining pluripotency. In addition, its ability to function as a pioneer factor enables the reprogramming of somatic cells back into a pluripotent state. To better understand the regulation of the Oct4-encoding gene (Pou5f1), the main genetic elements that regulate its expression in different states of pluripotency ought to be identified. While some elements have been well characterized for their ability to drive Pou5f1 expression, others have yet to be determined. In this work, we show that translocation of the Pou5f1 gene fragment purported to span all essential cis-elements, including the well-known distal and proximal enhancers (DE and PE), into the Rosa26 locus impairs the self-renewal of mouse embryonic stem cells (ESCs) in the naïve pluripotency state, as well as their further advancement through the formative and primed pluripotency states, inducing overall differentiation failure. These results suggest that regulatory elements located outside the previously determined Pou5f1 boundaries are critical for the proper spatiotemporal regulation of this gene during development, indicating the need for their better characterization. Full article
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Review

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14 pages, 3468 KiB  
Review
Notch and Wnt Signaling Modulation to Enhance DPSC Stemness and Therapeutic Potential
by Verónica Uribe-Etxebarria, Jose Ramon Pineda, Patricia García-Gallastegi, Alice Agliano, Fernando Unda and Gaskon Ibarretxe
Int. J. Mol. Sci. 2023, 24(8), 7389; https://doi.org/10.3390/ijms24087389 - 17 Apr 2023
Cited by 8 | Viewed by 2352
Abstract
The Dental Pulp of permanent human teeth is home to stem cells with remarkable multilineage differentiation ability: human Dental Pulp Stem Cells (DPSCs). These cells display a very notorious expression of pluripotency core factors, and the ability to give rise to mature cell [...] Read more.
The Dental Pulp of permanent human teeth is home to stem cells with remarkable multilineage differentiation ability: human Dental Pulp Stem Cells (DPSCs). These cells display a very notorious expression of pluripotency core factors, and the ability to give rise to mature cell lineages belonging to the three embryonic layers. For these reasons, several researchers in the field have long considered human DPSCs as pluripotent-like cells. Notably, some signaling pathways such as Notch and Wnt contribute to maintaining the stemness of these cells through a complex network involving metabolic and epigenetic regulatory mechanisms. The use of recombinant proteins and selective pharmacological modulators of Notch and Wnt pathways, together with serum-free media and appropriate scaffolds that allow the maintenance of the non-differentiated state of hDPSC cultures could be an interesting approach to optimize the potency of these stem cells, without a need for genetic modification. In this review, we describe and integrate findings that shed light on the mechanisms responsible for stemness maintenance of hDPSCs, and how these are regulated by Notch/Wnt activation, drawing some interesting parallelisms with pluripotent stem cells. We summarize previous work on the stem cell field that includes interactions between epigenetics, metabolic regulations, and pluripotency core factor expression in hDPSCs and other stem cell types. Full article
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