TGF-β Family Signaling in Embryonic and Somatic Stem-Cell Renewal and Differentiation

Mullen, Alan C.; Wrana, Jeffrey L.

doi:10.1101/cshperspect.a022186

Cited by 101 publications

(64 citation statements)

References 321 publications

(422 reference statements)

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“…The composition and function of the TGF-b signaling pathway and the extensive role of the TGF-b family in development, homeostasis, and diseases, including cancer, have been reviewed in detail elsewhere (David and Massagué , 2018;Mullen and Wrana, 2017;Oshimori and Fuchs, 2012). Here, we focus on the role of TGF-b in immune regulation and its relevance to cancer.…”

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor-β Signaling in Immunity and Cancer

2019

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Transforming growth factor (TGF)-b is a crucial enforcer of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Perturbations in TGF-b signaling underlie inflammatory diseases and promote tumor emergence. TGF-b is also central to immune suppression within the tumor microenvironment, and recent studies have revealed roles in tumor immune evasion and poor responses to cancer immunotherapy. Here, we present an overview of the complex biology of the TGF-b family and its context-dependent nature. Then, focusing on cancer, we discuss the roles of TGF-b signaling in distinct immune cell types and how this knowledge is being leveraged to unleash the immune system against the tumor.

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Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor-β Signaling in Immunity and Cancer

2019

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“…The upregulated genes in the TGFβ signaling pathway were BMPR1B, ID4, SMAD3 and TGFβ1, and there were also DEGs involved in the cell cycle pathway (CDKN1A) and signaling pathways regulating the pluripotency of stem cells (BMPR1B, ID4 and SMAD3). These genes are key regulators of cell proliferation, stem-cell state, differentiation, and apoptosis at the earliest stages of embryo development [62] and the TGFβ1 and SMAD3 are also key factors during embryo implantation [63,64]. The activation of the TGFβ-signaling pathway seems to be a response to cell stress and injury, as has been reported in epithelial cells [65].…”

Section: Discussionmentioning

confidence: 93%

Vitrification of in Vivo-derived Porcine Morulae and Blastocysts Alters Metabolic and Stress Response Pathway Alterations

Cuello¹,

Martínez²,

Cambra³

et al. 2020

Preprint

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BackgroundDespite reported promising farrowing rates after non-surgical and surgical transfers of vitrified in vivo-derived porcine morulae and blastocysts (range: 70-75%), their pregnancy loss is yet higher (10-20%) than it is for fresh embryos (< 2.5%). The present study was designed to investigate whether vitrification would affect the transcriptome of porcine morulae and blastocysts, using microarrays and qRT-PCR validation. Material and methods and resultsMorulae and blastocysts were collected from weaned sows (n=13) by laparotomy at Day 6 (Day 0=start of estrus). Of each embryo category, 50 morulae and 50 blastocysts were vitrified (Treatment group) while fresh morulae (n=40) and blastocysts (n=40) acted as control group. After one week of storage, vitrified embryos were cultured in vitrofor 24 h after warming. Non-vitrified morulae (n=40) and blastocysts (n=40), cultured in vitro for 24 h were used as controls. After the in vitro culture period, embryo viability was morphologically assessed. A total of 30 viable embryos per group and embryonic stage(three pools of 10), were subjected to gene expressionanalysis byusing a microarray approach. A fold change cut-off of ±1.5 and a p-unadjusted <0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed morulae and blastocysts were similar to those of the control (nearly 100%, n.s.).A total of 233 DEGs were identified in vitrified morulae (38 upregulated and 195 downregulated) and 105 (112 upregulated and 93 downregulated) in vitrified blastocysts compared to the control group.Transcriptome DEG profiles were dependent on developmental stage, and GO enrichment analysis mainly related DEGs tobiological processes.The vitrification/warming impact on morulae was mostly repression of gene expression with the exception of metabolism-related pathways. In the case of blastocysts, we noted the activation of the cell cycle, cellular senescence andof signaling pathways for TFGβ, p53, FoxO and MAPK. Disruption ofmetabolic-related pathways in morulae and steroid biosynthesis and gap junctions in blastocysts could be related to impaired embryo quality and developmental potential, despite the rather high post-warming survival rates seen in vitro.ConclusionIn conclusion, vitrification modified the transcriptome of in vivo-derived porcine morulae and blastocysts, resulting in moderate gene expression changes, which may disturb subsequent embryo development and pregnancy after embryo transfer.

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“…Protein expressions related to the ontology of the regulation of SMAD protein identified in the analysis of DEPs can be understood in the same context. Proteins involved in this ontology play a role in cell-fate decisions through the regulation of the TGF-beta pathway [ 39 ]. They could contribute to the maintenance of stem cell status by regulating cell proliferation and development.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of M-MSCs in DNCB-Induced Atopic Dermatitis Mice

et al. 2020

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Atopic dermatitis (AD) is an inflammatory skin disease caused by an imbalance between Th1 and Th2 cells. AD patients suffer from pruritus, excessive dryness, red or inflamed skin, and complications such as sleep disturbances and depression. Although there are currently many AD treatments available there are insufficient data on their long-term stability and comparative effects. Moreover, they have limitations due to various side effects. Multipotent mesenchymal stem cells (M-MSCs) might have potential for next-generation AD therapies. MSCs are capable of immune function regulation and local inflammatory response inhibition. M-MSCs, derived from human embryonic stem cells (hESC), additionally have a stable supply. In L507 antibody array, M-MSCs generally showed similar tendencies to bone marrow-derived mesenchymal stem cells (BM-MSCs), although the immunoregulatory function of M-MSCs seemed to be superior to BM-MSCs. Based on the characteristics of M-MSCs on immunoregulatory functions, we tested a M-MSC conditioned media concentrate (MCMC) in mice with AD lesions on their dorsal skin. MCMC significantly decreased RNA expression levels of inflammatory cytokines in the mouse dorsal skin. It also suppressed serum IgE levels. In addition, significant histopathologic alleviation was identified. In conclusion, secretions of M-MSCs have the potential to effectively improve AD-related inflammatory lesions. M-MSCs showed potential for use in next-generation AD treatment.

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TGF-β Family Signaling in Embryonic and Somatic Stem-Cell Renewal and Differentiation

Cited by 101 publications

References 321 publications

Transforming Growth Factor-β Signaling in Immunity and Cancer

Transforming Growth Factor-β Signaling in Immunity and Cancer

Vitrification of in Vivo-derived Porcine Morulae and Blastocysts Alters Metabolic and Stress Response Pathway Alterations

Anti-Inflammatory Effects of M-MSCs in DNCB-Induced Atopic Dermatitis Mice

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