Cdkn1a deletion or suppression by cyclic stretch enhance the osteogenic potential of bone marrow mesenchymal stem cell-derived cultures

Juran, Cassandra M.; Žvirblytė, Justina; Cheng-Campbell, Margareth; Blaber, Elizabeth A.; Almeida, Eduardo

doi:10.1016/j.scr.2021.102513

Cited by 10 publications

(6 citation statements)

References 51 publications

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“…TNIP2 activates NF-κB signalling, which induces osteoclastogenesis and triggers osteoporosis ( Fischer and Haffner-Luntzer, 2022 ; Wang et al, 2017 ). Cdkn1a codes for p21, which functions as a regulator of cell cycle progression at G1 and its deletion enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells in vitro ( Juran et al, 2021 ). Igf2bp1 codes for Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) which binds to the mRNA of certain genes, including IGF2 and β-actin, and regulates their transcription ( Yakar et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Signature of circulating small non-coding RNAs during early fracture healing in mice

Bourgery¹,

Ekholm²,

Hiltunen³

et al. 2022

Bone Reports

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Section: Resultsmentioning

confidence: 99%

Signature of circulating small non-coding RNAs during early fracture healing in mice

Bourgery¹,

Ekholm²,

Hiltunen³

et al. 2022

Bone Reports

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“…Investigations of mechanical unloading during spaceflight in microgravity have demonstrated the maintenance of “stemness” in ESCs, developmental EB spheroids, and lineage specific stem cells [ 22 , 23 , 32 , 33 ]. In contrast positive dynamic loading studies have shown that mechanical stimulation induces upregulation of proliferative and specialization gene pathways via independent molecular mechanisms [ 5 ]. Our study demonstrated that a 60-min HG pulse in day 9 EBs results in limited divergence in cell type assignment and transcriptomic signature from traditional static culture EBs.…”

Section: Discussionmentioning

confidence: 99%

“…To simulate physiologically relevant ranges of mechanical loads in cell cultures, various strategies have been used including applying cyclic stretch [ 5 ], or pulses of hydrostatic pressure [ 6 ], and hypergravity (HG) [ 7 ], that often result in enhanced cellular proliferation and differentiation effects. In the unique environment of space, free fall-induced weightlessness can modulate the intrinsic factors of tissue mechanical environment leading to reduced mechanical loads in tissue niche environments [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Differential Single Cell Responses of Embryonic Stem Cells Versus Embryoid Bodies to Gravity Mechanostimulation

Juran

Žvirblytė

Almeida

2022

Stem Cells and Development

Self Cite

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The forces generated by gravity have shaped life on Earth and impact gene expression and morphogenesis during early development. Conversely, disuse on Earth or during spaceflight, reduces normal mechanical loading of organisms, resulting in altered cell and tissue function. Although gravity mechanical loading in adult mammals is known to promote increased cell proliferation and differentiation, little is known about how distinct cell types respond to gravity mechanostimulation during early development. In this study we sought to understand, with single cell RNA-sequencing resolution, how a 60-min pulse of 50 g hypergravity (HG)/5 kPa hydrostatic pressure, influences transcriptomic regulation of developmental processes in the embryoid body (EB) model. Our study included both day-9 EBs and progenitor mouse embryonic stem cells (ESCs) with or without the HG pulse. Single cell t-distributed stochastic neighbor mapping shows limited transcriptome shifts in response to the HG pulse in either ESCs or EBs; this pulse however, induces greater positional shifts in EB mapping compared to ESCs, indicating the influence of mechanotransduction is more pronounced in later states of cell commitment within the developmental program. More specifically, HG resulted in upregulation of self-renewal and angiogenesis genes in ESCs, while in EBs, HG loading was associated with upregulation of Gene Ontology-pathways for multicellular development, mechanical signal transduction, and DNA damage repair. Cluster transcriptome analysis of the EBs show HG promotes maintenance of transitory cell phenotypes in early development; including EB cluster co-expression of markers for progenitor, post-implant epiblast, and primitive endoderm phenotypes with HG pulse but expression exclusivity in the non-pulsed clusters. Pseudotime analysis identified three branching cell types susceptible to HG induction of cell fate decisions. In totality, this study provides novel evidence that ESC maintenance and EB development can be regulated by gravity mechanostimulation and that stem cells committed to a differentiation program are more sensitive to gravity-induced changes to their transcriptome.

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“…TNIP2 activates NF-κB signalling, which induces osteoclastogenesis and triggers osteoporosis (Fischer and Haffner-Luntzer, 2022;Wang et al, 2017). Cdkn1a codes for p21, which functions as a regulator of cell cycle progression at G1 and its deletion enhances the osteogenic potential of bone marrowderived mesenchymal stem cells in vitro (Juran et al, 2021). Igf2bp1 codes for Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) which binds to the mRNA of certain genes, including IGF2 and β-actin, and regulates their transcription (Yakar et al, 2018).…”

Section: Tablementioning

confidence: 99%

Signature of Circulating Small Non-Coding RNAs During Early Fracture Healing in Mice

Bourgery,

Bendre,

Ekholm

et al. 2022

SSRN Journal

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Cdkn1a deletion or suppression by cyclic stretch enhance the osteogenic potential of bone marrow mesenchymal stem cell-derived cultures

Cited by 10 publications

References 51 publications

Signature of circulating small non-coding RNAs during early fracture healing in mice

Signature of circulating small non-coding RNAs during early fracture healing in mice

Differential Single Cell Responses of Embryonic Stem Cells Versus Embryoid Bodies to Gravity Mechanostimulation

Signature of Circulating Small Non-Coding RNAs During Early Fracture Healing in Mice

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