The Factors Governing Cell Fate and Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 6546

Special Issue Editor


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Guest Editor
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA
Interests: pluripotent stem cells; genome editing; disease modeling; cancer; metabolism; epigenetic; apoptosis

Special Issue Information

Dear Colleagues,

A fundamental goal of stem cell and developmental biology is to understand the mechanisms controlling cell fate decisions. Indeed, the development and regeneration of tissues rely on the proper fate commitment of stem cells. Cell fate is tightly regulated by a dynamic interplay between extrinsic and intrinsic factors. Every cell type has distinct metabolic demands related to their function and fate change is often accompanied by a metabolic switch. Recently, it has emerged that metabolism is not merely a consequence of cell fate changes, but is an important driver of cell fate decisions and lineage specification.

In this Special Issue, we welcome original research articles and reviews providing new insights into the factors that can control fate determination and in particular the role of metabolism and metabolites in cell fate decisions. This Special Issue will contribute to a better understanding of the role of metabolic changes in stem cell differentiation during normal organism development and in diseases.

Potential topics include but are not limited to the following:

  • Metabolomics analysis and the influence of metabolites on cell fate.
  • The involvement of organelles such as lysosomes and mitochondria in the metabolic regulation of cell fate.
  • Cell signaling regulators of metabolic state and fate decisions.
  • The impact of metabolism on cell fate in in vitro and in vivo models, including model organisms, rodents, and cells in 2D or 3D cultures.
  • The actors governing metabolic switches in pluripotent stem cells stages (naïve/primed PSC) and adult stem cells, as well as during reprogramming, direct differentiation and trans-differentiation.
  • The consequences of metabolic perturbations on cell fate in aging and in diseases such as obesity, degenerative disease, and cancer.

We are looking forward to your contribution to this Special Issue.

Dr. Julie Mathieu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cell fate
  • Metabolic reprogramming
  • Stem cells
  • Differentiation
  • Metabolites
  • Metabolomics
  • Metabolic disruption

Published Papers (2 papers)

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Research

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29 pages, 57331 KiB  
Article
The MicroRNA miR-277 Controls Physiology and Pathology of the Adult Drosophila Midgut by Regulating the Expression of Fatty Acid β-Oxidation-Related Genes in Intestinal Stem Cells
by Lisa Zipper, Sai Batchu, Nida Hatice Kaya, Zeus Andrea Antonello and Tobias Reiff
Metabolites 2022, 12(4), 315; https://doi.org/10.3390/metabo12040315 - 31 Mar 2022
Cited by 6 | Viewed by 3251
Abstract
Cell division, growth, and differentiation are energetically costly and dependent processes. In adult stem cell-based epithelia, cellular identity seems to be coupled with a cell’s metabolic profile and vice versa. It is thus tempting to speculate that resident stem cells have a distinct [...] Read more.
Cell division, growth, and differentiation are energetically costly and dependent processes. In adult stem cell-based epithelia, cellular identity seems to be coupled with a cell’s metabolic profile and vice versa. It is thus tempting to speculate that resident stem cells have a distinct metabolism, different from more committed progenitors and differentiated cells. Although investigated for many stem cell types in vitro, in vivo data of niche-residing stem cell metabolism is scarce. In adult epithelial tissues, stem cells, progenitor cells, and their progeny have very distinct functions and characteristics. In our study, we hypothesized and tested whether stem and progenitor cell types might have a distinctive metabolic profile in the intestinal lineage. Here, taking advantage of the genetically accessible adult Drosophila melanogaster intestine and the availability of ex vivo single cell sequencing data, we tested that hypothesis and investigated the metabolism of the intestinal lineage from stem cell (ISC) to differentiated epithelial cell in their native context under homeostatic conditions. Our initial in silico analysis of single cell RNAseq data and functional experiments identify the microRNA miR-277 as a posttranscriptional regulator of fatty acid β-oxidation (FAO) in the intestinal lineage. Low levels of miR-277 are detected in ISC and progressively rising miR-277 levels are found in progenitors during their growth and differentiation. Supporting this, miR-277-regulated fatty acid β-oxidation enzymes progressively declined from ISC towards more differentiated cells in our pseudotime single-cell RNAseq analysis and in functional assays on RNA and protein level. In addition, in silico clustering of single-cell RNAseq data based on metabolic genes validates that stem cells and progenitors belong to two independent clusters with well-defined metabolic characteristics. Furthermore, studying FAO genes in silico indicates that two populations of ISC exist that can be categorized in mitotically active and quiescent ISC, of which the latter relies on FAO genes. In line with an FAO dependency of ISC, forced expression of miR-277 phenocopies RNAi knockdown of FAO genes by reducing ISC size and subsequently resulting in stem cell death. We also investigated miR-277 effects on ISC in a benign and our newly developed CRISPR-Cas9-based colorectal cancer model and found effects on ISC survival, which as a consequence affects tumor growth, further underlining the importance of FAO in a pathological context. Taken together, our study provides new insights into the basal metabolic requirements of intestinal stem cell on β-oxidation of fatty acids evolutionarily implemented by a sole microRNA. Gaining knowledge about the metabolic differences and dependencies affecting the survival of two central and cancer-relevant cell populations in the fly and human intestine might reveal starting points for targeted combinatorial therapy in the hope for better treatment of colorectal cancer in the future. Full article
(This article belongs to the Special Issue The Factors Governing Cell Fate and Metabolism)
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Review

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14 pages, 1360 KiB  
Review
Succinate as a New Actor in Pluripotency and Early Development?
by Damien Detraux and Patricia Renard
Metabolites 2022, 12(7), 651; https://doi.org/10.3390/metabo12070651 - 15 Jul 2022
Cited by 2 | Viewed by 2790
Abstract
Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well [...] Read more.
Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well as a small subpopulation of cells that have reacquired features of the 2C-embryo (2C-like cells) in naïve mouse ESC culture. Altogether, these represent a continuum of distinct pluripotency stages, characterized by metabolic transitions, for which we propose a new role for a long-known metabolite: succinate. Mostly seen as the metabolite of the TCA, succinate is also at the crossroad of several mitochondrial biochemical pathways. Its role also extends far beyond the mitochondrion, as it can be secreted, modify proteins by lysine succinylation and inhibit the activity of alpha-ketoglutarate-dependent dioxygenases, such as prolyl hydroxylase (PHDs) or histone and DNA demethylases. When released in the extracellular compartment, succinate can trigger several key transduction pathways after binding to SUCNR1, a G-Protein Coupled Receptor. In this review, we highlight the different intra- and extracellular roles that succinate might play in the fields of early pluripotency and embryo development. Full article
(This article belongs to the Special Issue The Factors Governing Cell Fate and Metabolism)
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