Key transcription factors in the differentiation of mesenchymal stem cells

Almalki, Sami G.; Agrawal, Devendra K.

doi:10.1016/j.diff.2016.02.005

Cited by 323 publications

(257 citation statements)

References 132 publications

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“…For example, enforced expression of Gata4 plus two other transcription factors ( Sf1 and Dmrt1 ) can reprogram mouse fibroblasts into Leydig-like cells (Yang et al 2017). GATA6, like GATA4, has been implicated in mesenchymal stem cell function (Almalki & Agrawal 2016). The incomplete regeneration of Leydig cells that typifies our adenoviral injection model could reflect, at least partly, impaired Leydig stem cell function, and future experiments will explore this possibility.…”

Section: Discussionmentioning

confidence: 99%

Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

et al. 2017

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Testicular Leydig cells produce androgens essential for proper male reproductive development and fertility. Here, we describe a new Leydig cell ablation model based on Cre/Lox recombination of mouse Gata4 and Gata6, two genes implicated in the transcriptional regulation of steroidogenesis. The testicular interstitium of adult Gata4flox/flox;Gata6flox/flox mice was injected with adenoviral vectors encoding Cre + GFP (Ad-Cre-IRES-GFP) or GFP alone (Ad-GFP). The vectors efficiently and selectively transduced Leydig cells, as evidenced by GFP reporter expression. Three days after Ad-Cre-IRES-GFP injection, expression of androgen biosynthetic genes (Hsd3b1, Cyp17a1, Hsd17b3) was reduced, whereas expression of another Leydig cell marker, Insl3, was unchanged. Six days after Ad-Cre-IRES-GFP treatment, the testicular interstitium was devoid of Leydig cells, and there was a concomitant loss of all Leydig cell markers. Chromatin condensation, nuclear fragmentation, mitochondrial swelling, and other ultrastructural changes were evident in the degenerating Leydig cells. Liquid chromatography-tandem mass spectrometry demonstrated reduced levels of androstenedione and testosterone in testes from mice injected with Ad-Cre-IRES-GFP. Late effects of treatment included testicular atrophy, infertility, and the accumulation of lymphoid cells in the testicular interstitium. We conclude that adenoviral-mediated gene delivery is an expeditious way to probe Leydig cell function in vivo. Our findings reinforce the notion that GATA factors are key regulators of steroidogenesis and testicular somatic cell survival.

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Section: Discussionmentioning

confidence: 99%

Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

et al. 2017

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“…In differentiation process, differentially expression of transcription factors arises through specific signaling pathways or interaction with other transcription factors that act as co-regulators. Therefore, the differential expression of specific transcription factors, receptors, and signaling molecules during differentiation is critical for the understanding of the relationship between intracellular and extracellular signaling networks [47]. Further functional studies are undeniably needed to elucidate the mechanisms underlying the MSCs preconditioned by hypoxic stimulation for use in cardiac disease.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Cardiomyocyte Differentiation-Related Proteins in Rat Mesenchymal Stem Cells Exposed to Hypoxia

Choi¹,

Kim²,

Lee³

et al. 2016

Cell Physiol Biochem

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Background/Aims: It is known that mesenchymal stem cells (MSCs) can have variable responses to hypoxic conditions and that hypoxia may specifically stimulate differentiation into osteogenic, chondrogenic, or adipogenic cells. Based on our previous study, we hypothesized that hypoxia may also induce MSC differentiation into cardiomyocytes and/or cells with comparable phenotypes. Methods: The differences in the proteomes were specifically investigated in bone marrow-derived rat MSCs (BM-rMSCs) under normoxic and hypoxic conditions using 2-DE combined with a MALDI-TOF-MS analysis and western blot analysis. In addition, genetic and/or proteomic interactions were assessed using a String network analysis. Results: Among the 35 markedly changed spots from a total of 393 matched spots, 24 were highly up-regulated and 11 were significantly down-regulated in hypoxic rMSCs based on a proteomic analysis. Although hypoxia failed to induce the direct differentiation of rMSCs into cardiomyocytes, several cardiomyocyte differentiation-related genes and proteins were significantly increased by hypoxic stress. Conclusion: We found that BM-rMSCs alter their expression of several cardiomyocyte differentiation-related genes and proteins under hypoxic conditions, and we examined the interactions between these genes and/or proteins, providing new insights for the applicability of MSCs preconditioned by hypoxic stimulation for use in cardiac diseases.

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“…The lack of blood and oxygen supply in the damaged area is also a possible cause of cell death [49]. However, a small portion of MSCs are able to temporarily escape from death, migrate to the injured site, and successfully differentiate into functional cells to participate in tissue repair [50]. Another possible route is that MSCs can quickly migrate to the damaged site, affecting other cells through paracrine effects, and participate in the process of tissue repair and immune regulation.…”

Section: Discussionmentioning

confidence: 99%

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques

Wang

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. Methods: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. Results: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP⁺/α-SMA⁺- and GFP⁺/VIM⁺-cell numbers decreased gradually with healing time, α-SMA⁺- and VIM⁺-cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. Conclusion: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.

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Key transcription factors in the differentiation of mesenchymal stem cells

Cited by 323 publications

References 132 publications

Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

Alterations in Cardiomyocyte Differentiation-Related Proteins in Rat Mesenchymal Stem Cells Exposed to Hypoxia

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques

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