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Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 23801

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Dr. Cristi L. Galindo

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Department of Biology, Western Kentucky University, Bowling Green, KY 42101, USA
Interests: muscular dystrophy; Duchenne; BDNF; neuregulin; ErbB3; cardiac fibrosis; TrkB; skeletal muscle
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Dear Colleagues,

Recent advances in biotechnologies have increased our breadth of knowledge regarding intracellular signaling and molecular biology more generally, and their associated signaling networks have likewise grown in scope and complexity. For many ligands, receptors, and intracellular signaling partners, downstream molecular processes and functions have essentially left the “canonical” realm by any reasonable definition to encompass multiple, interlinking networks across numerous cell types and crossing the organ differentiation. The original organ differentiation has thus become blurred, shifting the focus to system omics and necessitating a “thinking outside of the organ” mentality. Therefore, this Special Issue is dedicated to presenting the latest research on biomedical-relevant biomolecules, such as multipotent and multisystem effectors of consequence crossing organs such as in brain, liver, heart, lung, skin, muscle, corneal ulcer, tendon, bone, and human cells or animal models.

Dr. Cristi L. Galindo
Guest Editor

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Keywords

cross pathway
interlinking networks
organ differentiation
multipotent
biomolecules
multisystem
signaling pathways
regulation
animal models
human cells

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Published Papers (7 papers)

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Research

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7 pages, 914 KiB

Open AccessCommunication

Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema

by Shin Ohta, Akihiko Tanaka, Tomoko Okazaki, Hatsuko Mikuni, Tomoki Uno, Yoshitaka Uchida, Tomoyuki Kimura, Yosuke Fukuda, Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Shintaro Suzuki and Hironori Sagara

Curr. Issues Mol. Biol. 2022, 44(9), 3923-3929; https://doi.org/10.3390/cimb44090269 - 29 Aug 2022

Viewed by 1708

Abstract

Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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10 pages, 1437 KiB

Open AccessArticle

TNF-α Suppresses Apelin Receptor Expression in Mouse Quadriceps Femoris-Derived Cells

by Tomohisa Koyama, Kentaro Uchida, Makoto Itakura, Masayuki Miyagi, Ryo Tazawa, Gen Inoue, Kensuke Fukushima, Yoshihisa Ohashi, Ayumi Tsukada and Masashi Takaso

Curr. Issues Mol. Biol. 2022, 44(7), 3146-3155; https://doi.org/10.3390/cimb44070217 - 8 Jul 2022

Viewed by 2030

Abstract

Expression of the apelin receptor, APJ, in skeletal muscle (SM) is known to decrease with age, but the underlying mechanism remains unclear. Increased tumor necrosis factor (TNF)-α levels are observed in SM with age and are associated with muscle atrophy. To investigate the possible interconnection between TNF-α elevation and APJ reduction with aging, we investigated the effect of TNF-α on APJ expression in cells derived from the quadriceps femoris of C57BL/6J mice. Expression of Tnfa and Apj in the quadriceps femoris was compared between 4- (young) and 24-month-old (old) C57BL/6J mice (n = 10 each) using qPCR. Additionally, APJ-positive cells and TNF-α protein were analyzed by flow cytometry and Western blotting, respectively. Further, quadricep-derived cells were exposed to 0 (control) or 25 ng/mL TNF-α, and the effect on Apj expression was examined by qRT-PCR. Apj expression and the ratio of APJ-positive cells among quadricep cells were significantly lower in old compared to young mice. In contrast, levels of Tnfa mRNA and TNF-α protein were significantly elevated in old compared to young mice. Exposing young and old derived quadricep cells to TNF-α for 8 and 24 h caused Apj levels to significantly decrease. TNF-α suppresses APJ expression in muscle cells in vitro. The increase in TNF-α observed in SM with age may induce a decrease in APJ expression. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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15 pages, 3591 KiB

Open AccessArticle

Characterization of Insulin-like Peptide (ILP) and Its Potential Role in Ovarian Development of the Cuttlefish Sepiella japonica

by Zhenming Lü, Chenghao Yao, Shijie Zhao, Yao Zhang, Li Gong, Bingjian Liu and Liqin Liu

Curr. Issues Mol. Biol. 2022, 44(6), 2490-2504; https://doi.org/10.3390/cimb44060170 - 27 May 2022

Cited by 6 | Viewed by 2258

Abstract

The insulin-like peptide (ILP) family is well known for regulating reproduction in invertebrates, while its role in mollusks remains largely unknown. In this study, we first isolated and characterized the ILP gene in the cuttlefish Sepiella japonica. The full-length SjILP cDNA obtained was 926 bp and encoded a precursor protein of 161 amino acids. The precursor protein consisted of a signal peptide, a B chain, a C-peptide, and an A chain. It possessed the typical features of ILP proteins, including two cleavage sites (KR) and eight conserved cysteines. To define the function of SjILP, the expression of SjILP in different tissues and ovarian development stages were analyzed using qRT-PCR. SjILP was mainly expressed in the ovary, and its gene expression correlated with ovarian development. Furthermore, silencing SjILP using RNA interference (RNAi) dramatically decreased the expression levels of four ovarian-development-related genes (vitellogenin1, vitellogenin2, cathepsin L1-like, and follistatin). These data suggest the critical role of SjILP in the regulation of ovarian development in S. japonica. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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16 pages, 7300 KiB

Open AccessArticle

Time-Series Clustering of lncRNA-mRNA Expression during the Adipogenic Transdifferentiation of Porcine Skeletal Muscle Satellite Cells

by Xiaoyu Qiu, Guangliang Gao, Lei Du, Jing Wang, Qi Wang, Feiyun Yang, Xiaorong Zhou, Dingbiao Long, Jinxiu Huang, Zuohua Liu and Renli Qi

Curr. Issues Mol. Biol. 2022, 44(5), 2038-2053; https://doi.org/10.3390/cimb44050138 - 6 May 2022

Cited by 5 | Viewed by 2846

Abstract

Skeletal muscle satellite cells (SMSCs), which are multifunctional muscle-derived stem cells, can differentiate into adipocytes. Long-chain non-coding RNA (lncRNA) has diverse biological functions, including the regulation of gene expression, chromosome silencing, and nuclear transport. However, the regulatory roles and mechanism of lncRNA during adipogenic transdifferentiation in muscle cells have not been thoroughly investigated. Here, porcine SMSCs were isolated, cultured, and induced for adipogenic differentiation. The expressions of lncRNA and mRNA at different time points during transdifferentiation were analysed using RNA-seq analysis. In total, 1005 lncRNAs and 7671 mRNAs showed significant changes in expression at differential differentiation stages. Time-series expression analysis showed that the differentially expressed (DE) lncRNAs and mRNAs were clustered into 5 and 11 different profiles with different changes, respectively. GO, KEGG, and REACTOME enrichment analyses revealed that DE mRNAs with increased expressions during the trans-differentiation were mainly enriched in the pathways for lipid metabolism and fat cell differentiation. The genes with decreased expressions were mainly enriched in the regulation of cell cycle and genetic information processing. In addition, 1883 DE mRNAs were regulated by 193 DE lncRNAs, and these genes were related to the controlling in cell cycle mainly. Notably, three genes in the fatty acid binding protein (FABP) family significantly and continuously increased during trans-differentiation, and 15, 13, and 11 lncRNAs may target FABP3, FABP4, and FABP5 genes by cis- or trans-regulation, respectively. In conclusion, these studies identify a set of new potential regulator for adipogenesis and cell fate and help us in better understanding the molecular mechanisms of trans-differentiation. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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15 pages, 31439 KiB

Open AccessArticle

The Transcriptional Cell Atlas of Testis Development in Sheep at Pre-Sexual Maturity

by Yi Wu, Tingting Guo, Jianye Li, Chune Niu, Weibo Sun, Shaohua Zhu, Hongchang Zhao, Guoyan Qiao, Mei Han, Xue He, Zengkui Lu, Chao Yuan, Jianlin Han, Jianbin Liu, Bohui Yang and Yaojing Yue

Curr. Issues Mol. Biol. 2022, 44(2), 483-497; https://doi.org/10.3390/cimb44020033 - 19 Jan 2022

Cited by 10 | Viewed by 3627

Abstract

Sheep testes undergo a dramatic rate of development with structural changes during pre-sexual maturity, including the proliferation and maturation of somatic niche cells and the initiation of spermatogenesis. To explore this complex process, 12,843 testicular cells from three males at pre-sexual maturity (three-month-old) were sequenced using the 10× Genomics Chromium^TM single-cell RNA-seq (scRNA-seq) technology. Nine testicular somatic cell types (Sertoli cells, myoid cells, monocytes, macrophages, Leydig cells, dendritic cells, endothelial cells, smooth muscle cells, and leukocytes) and an unknown cell cluster were observed. In particular, five male germ cell types (including two types of undifferentiated spermatogonia (A_pale and A_dark), primary spermatocytes, secondary spermatocytes, and sperm cells) were identified. Interestingly, A_pale and A_dark were found to be two distinct states of undifferentiated spermatogonia. Further analysis identified specific marker genes, including UCHL1, DDX4, SOHLH1, KITLG, and PCNA, in the germ cells at different states of differentiation. The study revealed significant changes in germline stem cells at pre-sexual maturation, paving the way to explore the candidate factors and pathways for the regulation of germ and somatic cells, and to provide us with opportunities for the establishment of livestock stem cell breeding programs. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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11 pages, 2942 KiB

Open AccessArticle

Bone Morphogenetic Protein 4 (BMP4) Enhances the Differentiation of Human Induced Pluripotent Stem Cells into Limbal Progenitor Cells

by Hyun Soo Lee, Jeewon Mok and Choun-Ki Joo

Curr. Issues Mol. Biol. 2021, 43(3), 2124-2134; https://doi.org/10.3390/cimb43030147 - 29 Nov 2021

Cited by 6 | Viewed by 3330

Abstract

Corneal epithelium maintains visual acuity and is regenerated by the proliferation and differentiation of limbal progenitor cells. Transplantation of human limbal progenitor cells could restore the integrity and functionality of the corneal surface in patients with limbal stem cell deficiency. However, multiple protocols are employed to differentiate human induced pluripotent stem (iPS) cells into corneal epithelium or limbal progenitor cells. The aim of this study was to optimize a protocol that uses bone morphogenetic protein 4 (BMP4) and limbal cell-specific medium. Human dermal fibroblast-derived iPS cells were differentiated into limbal progenitor cells using limbal cell-specific (PI) medium and varying doses (1, 10, and 50 ng/mL) and durations (1, 3, and 10 days) of BMP4 treatment. Differentiated human iPS cells were analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemical studies at 2 or 4 weeks after BMP4 treatment. Culturing human dermal fibroblast-derived iPS cells in limbal cell-specific medium and BMP4 gave rise to limbal progenitor and corneal epithelial-like cells. The optimal protocol of 10 ng/mL and three days of BMP4 treatment elicited significantly higher limbal progenitor marker (ABCG2, ∆Np63α) expression and less corneal epithelial cell marker (CK3, CK12) expression than the other combinations of BMP4 dose and duration. In conclusion, this study identified a successful reprogramming strategy to induce limbal progenitor cells from human iPS cells using limbal cell-specific medium and BMP4. Additionally, our experiments indicate that the optimal BMP4 dose and duration favor limbal progenitor cell differentiation over corneal epithelial cells and maintain the phenotype of limbal stem cells. These findings contribute to the development of therapies for limbal stem cell deficiency disorders. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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Review

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23 pages, 1938 KiB

Open AccessReview

A Glance at the Molecules That Regulate Oligodendrocyte Myelination

by Shunqi Wang, Yingxing Wang and Suqi Zou

Curr. Issues Mol. Biol. 2022, 44(5), 2194-2216; https://doi.org/10.3390/cimb44050149 - 15 May 2022

Cited by 10 | Viewed by 6982

Abstract

Oligodendrocyte (OL) myelination is a critical process for the neuronal axon function in the central nervous system. After demyelination occurs because of pathophysiology, remyelination makes repairs similar to myelination. Proliferation and differentiation are the two main stages in OL myelination, and most factors commonly play converse roles in these two stages, except for a few factors and signaling pathways, such as OLIG2 (Oligodendrocyte transcription factor 2). Moreover, some OL maturation gene mutations induce hypomyelination or hypermyelination without an obvious function in proliferation and differentiation. Herein, three types of factors regulating myelination are reviewed in sequence. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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