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Advances in Stem Cells and Organoid Development: Exploring Molecular, Metabolic and Electro-Synaptic Mechanisms Using Systems Approach

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: 30 June 2024 | Viewed by 9199

Special Issue Editors


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Guest Editor
1. Department of Pathology and Anatomical Sciences, Jacobs School of Medicine & Biomedical Science, State University of New York, University at Buffalo, Buffalo, NY, USA
2. Department of Biomedical Engineering, State University of New York, University at Buffalo, Buffalo, NY, USA
Interests: cell biology; stem cells; genomics; development; neuroscience; systems biology

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Guest Editor
Neuroengineering and Informatics for Rehabilitation and Simulation-Based Learning (NIRSlearn), University of Lincoln, Lincoln LN6 7TS, UK
Interests: neuroengineering; neural interfaces; neural circuits; neurotechnology; microfluidics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stem cell technologies have highlighted the development, pathologies, and control of stem cells, organoids and 3D cancer cultures at the new, global systems levels. This has become feasible due to recent developments in high-throughput genomics, proteomics, electro-synaptomics and nanophotonics engineering. This Special Issue will publish current research in these areas and propose future studies to ultimately integrate genome–neuronal and genome–cancer models constructed by correlating genomic topology, gene activity networks, protein networks and resultant cellular and neuronal networks.

Prof. Dr. Michal K. Stachowiak
Dr. Anirban Dutta
Guest Editors

Manuscript Submission Information

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Keywords

  • stem cells
  • genome
  • proteomics
  • organoids
  • systems

Published Papers (3 papers)

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Research

18 pages, 2585 KiB  
Article
Engineering Nanofiber Scaffolds with Biomimetic Cues for Differentiation of Skin-Derived Neural Crest-like Stem Cells to Schwann Cells
by Ashis Kumar Podder, Mohamed Alaa Mohamed, Georgios Tseropoulos, Bita Nasiri and Stelios T. Andreadis
Int. J. Mol. Sci. 2022, 23(18), 10834; https://doi.org/10.3390/ijms231810834 - 16 Sep 2022
Cited by 4 | Viewed by 1743
Abstract
Our laboratory reported the derivation of neural crest stem cell (NCSC)-like cells from the interfollicular epidermis of the neonatal and adult epidermis. These keratinocyte (KC)-derived Neural Crest (NC)-like cells (KC-NC) could differentiate into functional neurons, Schwann cells (SC), melanocytes, and smooth muscle cells [...] Read more.
Our laboratory reported the derivation of neural crest stem cell (NCSC)-like cells from the interfollicular epidermis of the neonatal and adult epidermis. These keratinocyte (KC)-derived Neural Crest (NC)-like cells (KC-NC) could differentiate into functional neurons, Schwann cells (SC), melanocytes, and smooth muscle cells in vitro. Most notably, KC-NC migrated along stereotypical pathways and gave rise to multiple NC derivatives upon transplantation into chicken embryos, corroborating their NC phenotype. Here, we present an innovative design concept for developing anisotropically aligned scaffolds with chemically immobilized biological cues to promote differentiation of the KC-NC towards the SC. Specifically, we designed electrospun nanofibers and examined the effect of bioactive cues in guiding KC-NC differentiation into SC. KC-NC attached to nanofibers and adopted a spindle-like morphology, similar to the native extracellular matrix (ECM) microarchitecture of the peripheral nerves. Immobilization of biological cues, especially Neuregulin1 (NRG1) promoted the differentiation of KC-NC into the SC lineage. This study suggests that poly-ε-caprolactone (PCL) nanofibers decorated with topographical and cell-instructive cues may be a potential platform for enhancing KC-NC differentiation toward SC. Full article
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20 pages, 37129 KiB  
Article
Global Transcriptional Analyses of the Wnt-Induced Development of Neural Stem Cells from Human Pluripotent Stem Cells
by Bing-Chun Liu, Fang-Yuan Liu, Xin-Yue Gao, Yang-Lin Chen, Qiao-Qiao Meng, Yong-Li Song, Xi-He Li and Si-Qin Bao
Int. J. Mol. Sci. 2021, 22(14), 7473; https://doi.org/10.3390/ijms22147473 - 12 Jul 2021
Cited by 8 | Viewed by 3218
Abstract
The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional [...] Read more.
The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional pathways that mediate Wnt-induced hPSCs to NSCs differentiation is vital for understanding the global genomic mechanisms of the development of NSCs and, potentially, the creation of new protocols in regenerative medicine. To understand the genomic mechanism of Wnt signaling during NSCs development, we treated hPSCs with Wnt activator (CHIR-99021) and leukemia inhibitory factor (LIF) in a chemically defined medium (N2B27) to induce NSCs, referred to as CLNSCs. The CLNSCs were subcultured for more than 40 passages in vitro; were positive for AP staining; expressed neural progenitor markers such as NESTIN, PAX6, SOX2, and SOX1; and were able to differentiate into three neural lineage cells: neurons, astrocytes, and oligodendrocytes in vitro. Our transcriptome analyses revealed that the Wnt and Hedgehog signaling pathways regulate hPSCs cell fate decisions for neural lineages and maintain the self-renewal of CLNSCs. One interesting network could be the deregulation of the Wnt/β-catenin signaling pathway in CLNSCs via the downregulation of c-MYC, which may promote exit from pluripotency and neural differentiation. The Wnt-induced spinal markers HOXA1-4, HOXA7, HOXB1-4, and HOXC4 were increased, however, the brain markers FOXG1 and OTX2, were absent in the CLNSCs, indicating that CLNSCs have partial spinal cord properties. Finally, a CLNSC simple culture condition, when applied to hPSCs, supports the generation of NSCs, and provides a new and efficient cell model with which to untangle the mechanisms during neurogenesis. Full article
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40 pages, 17022 KiB  
Article
Global Genome Conformational Programming during Neuronal Development Is Associated with CTCF and Nuclear FGFR1—The Genome Archipelago Model
by Brandon Decker, Michal Liput, Hussam Abdellatif, Donald Yergeau, Yongho Bae, Josep M. Jornet, Ewa K. Stachowiak and Michal K. Stachowiak
Int. J. Mol. Sci. 2021, 22(1), 347; https://doi.org/10.3390/ijms22010347 - 31 Dec 2020
Cited by 8 | Viewed by 3937
Abstract
During the development of mouse embryonic stem cells (ESC) to neuronal committed cells (NCC), coordinated changes in the expression of 2851 genes take place, mediated by the nuclear form of FGFR1. In this paper, widespread differences are demonstrated in the ESC and NCC [...] Read more.
During the development of mouse embryonic stem cells (ESC) to neuronal committed cells (NCC), coordinated changes in the expression of 2851 genes take place, mediated by the nuclear form of FGFR1. In this paper, widespread differences are demonstrated in the ESC and NCC inter- and intra-chromosomal interactions, chromatin looping, the formation of CTCF- and nFGFR1-linked Topologically Associating Domains (TADs) on a genome-wide scale and in exemplary HoxA-D loci. The analysis centered on HoxA cluster shows that blocking FGFR1 disrupts the loop formation. FGFR1 binding and genome locales are predictive of the genome interactions; likewise, chromatin interactions along with nFGFR1 binding are predictive of the genome function and correlate with genome regulatory attributes and gene expression. This study advances a topologically integrated genome archipelago model that undergoes structural transformations through the formation of nFGFR1-associated TADs. The makeover of the TAD islands serves to recruit distinct ontogenic programs during the development of the ESC to NCC. Full article
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