FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins

Awan, Baarkullah; Turkov, David; Schumacher, Cameron; Jacobo, Antonio; McEnerney, Amber; Ramsey, Ashley; Xu, Gege; Park, Dayoung; Kalomoiris, Stefanos; Yao, Wei; Jao, Li-En; Allende, Miguel L.; Lebrilla, Carlito B.; Fierro, Fernando A.

doi:10.1016/j.stemcr.2018.06.007

Cited by 31 publications

(39 citation statements)

References 35 publications

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“…It has previously been reported that in MSCs treated with FGF‐2 in 2D, FGF‐2 treatment upregulates genes associated with cell proliferation and downregulates genes associated with collagen‐related processes in MSCs. [ 14 ] Among the 20 most overrepresented GO terms associated with MSCs treated with FGF‐2 here, we found many terms related to mitosis and cell division, clearly showing the proliferative effect of FGF‐2 (Figure 4b). On the other hand, GO terms that were overrepresented in the absence of FGF‐2 almost all relate to the ECM (Figure 4c).…”

Section: Resultsmentioning

confidence: 86%

“…On the other hand, GO terms that were overrepresented in the absence of FGF‐2 almost all relate to the ECM (Figure 4c). We compared our dataset representing 3D‐cultured MSCs to the published RNAseq dataset of MSCs treated with FGF‐2 in 2D, [ 14 ] and found a positive correlation between both datasets (Figure S5a, Supporting Information). However, 3D culture induced larger gene expression changes than when MSCs were cultured in 2D, which were mainly related to cell proliferation (induced by FGF‐2) and ECM (reduced by FGF‐2) GO terms (Figure S5b,c, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…DEG genes were compared with expression changes in a published RNA sequencing dataset (GEO: GSE115240) of MSCs cultured in 2D and treated with or without FGF‐2 (10 ng mL −1 , 24 h). [ 14 ] Genes were classed as significantly differentially expressed in the 2D dataset provided the Bonferoni‐corrected p ‐value <0.05. Genes that were significantly differentially expressed in 3D but not 2D were analyzed for significantly represented terms as described above.…”

Section: Methodsmentioning

confidence: 99%

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Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF‐2

Horton

Vallmajó-Martín

Martín

et al. 2020

Adv Healthcare Materials

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In native tissues, the interaction between cells and the surrounding extracellular matrix (ECM) is reciprocal, as cells not only receive signals from the ECM but also actively remodel it through secretion of cell‐derived ECM. However, very little is known about the reciprocal interaction between cells and their secreted ECM within synthetic biomaterials that mimic the ECM for use in engineering of tissues for regenerative medicine or as tissue models. Here, poly(ethylene glycol) (PEG) hydrogels with fully defined biomaterial properties are used to investigate the emerging role of cell‐derived ECM on culture outcomes. It is shown that human mesenchymal stromal cells (MSCs) secrete ECM proteins into the pericellular space early after encapsulation and that, even in the absence of material‐presented cell adhesion motifs, cell‐derived fibronectin enables cell spreading. Then, it is investigated how different culture conditions influence MSC ECM expression in hydrogels. Most strikingly, it is found by RNA sequencing that the fibroblast growth factor 2 (FGF‐2) changes ECM gene expression and, in particular, decreases the expression of structural ECM components including fibrillar collagens. In summary, this work shows that cell‐derived ECM is a guiding cue in 3D hydrogels and that FGF‐2 is a potentially important ECM regulator within bioengineered cell and tissue systems.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF‐2

Horton

Vallmajó-Martín

Martín

et al. 2020

Adv Healthcare Materials

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“…During bone remodeling and fractured-bone regeneration, MSCs migrate to the bone surface or fracture site and then differentiate into OBs to reconstruct the bone [76], subsequent to the osteoclastic resorptive phase. It has been well demonstrated that local growth factors and signals play important roles in the recruitment and commitment of MSCs [77], such as the bone morphogenetic protein (BMP) family [78], insulin-like growth factor (IGF) [79,80], TGF-β [68,81], fibroblast growth factor 2 (FGF-2) [82], vascular endothelial growth factors (VEGF) [78], and platelet-derived growth factors (PDGFs) [83,84]. Moreover, emerging evidence showed that many of these local factors are associated with the viability and activity of OCs [17,20,54].…”

Section: Effect Of Osteoclasts On Mesenchymal Stem Cell Recruitment Amentioning

confidence: 99%

Friend or Foe? Essential Roles of Osteoclast in Maintaining Skeletal Health

Wang

Yang

Xiao

et al. 2020

BioMed Research International

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Heightened activity of osteoclast is considered to be the culprit in breaking the balance during bone remodeling in pathological conditions, such as osteoporosis. As a “foe” of skeletal health, many antiosteoporosis therapies aim to inhibit osteoclastogenesis. However, bone remodeling is a dynamic process that requires the subtle coordination of osteoclasts and osteoblasts. Severe suppression of osteoclast differentiation will impair bone formation because of the coupling effect. Thus, understanding the complex roles of osteoclast in maintaining proper bone remodeling is highly warranted to develop better management of osteoporosis. This review aimed to determine the varied roles of osteoclasts in maintaining skeletal health and to highlight the positive roles of osteoclasts in maintaining normal bone remodeling. Generally, osteoclasts interact with osteocytes to initiate targeted bone remodeling and have crosstalk with mesenchymal stem cells and osteoblasts via secreted factors or cell-cell contact to promote bone formation. We believe that a better outcome of bone remodeling disorders will be achieved when proper strategies are made to coordinate osteoclasts and osteoblasts in managing such disorders.

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“…The two short-term samples also shared common transcripts, including Irgm2, Igtp, D8Ertd82e, Bcl3, and Serpina3f, which were further elevated compared to their corresponding controls. Most of these common genes participate in immune and complement pathways [18][19][20] .…”

Section: Resultsmentioning

confidence: 99%

Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration

Wang

Rhee

Pellegrini

et al. 2020

Sci Rep

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ciliary neurotrophic factor (cntf) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, we performed high-throughput RnA sequencing analyses using the Rds/Prph2 (P216L) transgenic mouse as a preclinical model for retinitis pigmentosa. In the absence of cntf treatment, transcriptome alterations were detected at the onset of rod degeneration compared with wild type mice, including reduction of key photoreceptor transcription factors Crx, Nrl, and rod phototransduction genes. Short-term CNTF treatments caused further declines of photoreceptor transcription factors accompanied by marked decreases of both rod-and cone-specific gene expression. in addition, cntf triggered acute elevation of transcripts in the innate immune system and growth factor signaling. These immune responses were sustained after long-term CNTF exposures that also affected neuronal transmission and metabolism. Comparisons of transcriptomes also uncovered common pathways shared with other retinal degeneration models. Cross referencing bulk RNA-seq with single-cell RnA-seq data revealed the cntf responsive cell types, including Müller glia, rod and cone photoreceptors, and bipolar cells. Together, these results demonstrate the influence of exogenous cntf on the retinal transcriptome landscape and illuminate likely cntf impacts in degenerating human retinas. Retinal degeneration (RD) is known as an irreversible, progressive neurologic disorder caused by genetic mutations and/or environmental or pathological damage to the retina. One therapeutic strategy to attenuate vision loss in disease conditions is treating the retina with neuroprotective agents that promote neuronal viability. Ciliary neurotrophic factor (CNTF) has been shown to be a potent neuroprotective agent for various types of retinal degenerations, including those caused by gene mutations, light-induced damage, and physical injury 1. Since CNTF enhances the survival of both photoreceptors and retinal ganglion cells, the two major cell classes damaged in retinal degenerative diseases, a CNTF-based therapy has been developed and tested in several clinical trials. To date, outcomes of the trials for retinitis pigmentosa, geographic atrophy, and achromatopsia have not demonstrated sufficient therapeutic benefits for human patients 2-5. However, CNTF therapy for macular telangiectasia type 2 has shown efficacy 6,7 , and a clinical trial for the second largest blinding disease glaucoma 8 is ongoing (https://clinicaltrials.gov/ct2/show/NCT01408472). To shed light on the molecular and cellular mechanisms of CNTF-mediated neuroprotection, we have delivered the same secreted recombinant CNTF used in human trials to a mouse model expressing the Rds/peripherin2 (Prph2) transgene with the P216L mutation 9. Pheripherin2 is a structural protein of the photoreceptor outer segment disc, and over 80 PRPH2 pathological mutations have been linked to RD, with...

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FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins

Cited by 31 publications

References 35 publications

Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF‐2

Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF‐2

Friend or Foe? Essential Roles of Osteoclast in Maintaining Skeletal Health

Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration

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