An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2

Cho, Ara; Park, Se-Ra; Kim, Chang Woo; Nam, Seungyoon; Lim, Seung Joo; Park, Chan Hum; Lee, Hwa-Yong; Hong, In–Sun

doi:10.1016/j.ymthe.2019.04.019

Cited by 32 publications

(22 citation statements)

References 48 publications

(51 reference statements)

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“…3A). Among them, FOXA1, PLAT, CD44, FGF5, DIO2 and other genes are upregulated, whereas PLCB1, SETBP1, EHD3, ZNF423, PHGDH and other genes are downregulated in multiple senescence systems(Chan et al, 2019; Cho et al, 2019; Galanos et al, 2016; Hari et al, 2019; Hernandez-Segura et al, 2017; Komseli et al, 2018; Lau, Porciuncula, Yu, Iwakura, & David, 2019; Leveque et al, 2019; Q. Li et al, 2013; Limbad et al, 2020; Lowe & Raj, 2014; Nagano et al, 2016; Pan et al, 2019; Pantazi et al, 2019; Suwan et al, 2009; Wu, Pepowski, Takahashi, & Kron, 2019; Zhou et al, 2010), as are consistent with our results.…”

Section: Resultssupporting

confidence: 92%

ATF3 drives senescence by reconstructing accessible chromatin profiles

Zhang

Guan

et al. 2020

Preprint

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Chromatin architecture and gene expression profile undergo tremendous reestablishment during senescence. However, the regulatory mechanism between chromatin reconstruction and gene expression in senescence remain elusive. The chromatin accessibility is an excellent perspective to reveal the latent regulatory elements. Thus, we depicted the landscapes of chromatin accessibility and gene expression during HUVECs senescence. We found that chromatin accessibilities are re-distributed during senescence. The senescence related increased accessible regions (IARs) and the decreased accessible regions (DARs) are mainly distributed in distal intergenic regions. The DARs are correlated with the function declines caused by senescence, whereas the IARs are involved in the regulation for senescence program. Moreover, the heterochromatin contributes most of IARs in senescent cells. We identified that the AP-1 transcription factors, especially ATF3 is responsible for driving chromatin accessibility reconstruction in IARs. In particular, DNA methylation is negatively correlated with chromatin accessibility during senescence. AP-1 motifs with low DNA methylation may improve their binding affinity in IARs and further opens the chromatin nearby. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program. And we identified a cellular senescence regulator, AP-1, which promotes senescence through organizing the accessibility profile in IARs.

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Section: Resultssupporting

confidence: 92%

ATF3 drives senescence by reconstructing accessible chromatin profiles

Zhang

Guan

et al. 2020

Preprint

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“…Another notable finding of this study is that we identify the role of SHH signaling in modulating cellular senescence, proliferation, and the differentiation propensity of iPSC‐MSCs. Consistent with our finding, a previous study has reported that activities of SHH signaling molecules decrease with cell aging, and the aging‐related decline in SHH signaling integrity leads to loss and dysfunction of endometrial stem cells 43 . Our study further reveals that SHH signaling is a downstream pathway regulated by GATA6.…”

Section: Discussionsupporting

confidence: 92%

“…finding, a previous study has reported that activities of SHH signaling molecules decrease with cell aging, and the aging-related decline in SHH signaling integrity leads to loss and dysfunction of endometrial stem cells. 43 The discrepancy on which of the p53 and p16 INK4A pathways is engaged in the regulation of cellular senescence may be explained by the use of different MSC types. 50 Differences in the growth rate between SF-MSCs and iPSC-MSCs shown in this study, consistent with the previous finding, 10,51 is likely the result of increased telomerase activity and longer telomere length in iPSC-MSCs compared with those in their parental SF-MSCs.…”

Section: Discussionmentioning

confidence: 99%

GATA6 regulates aging of human mesenchymal stem/stromal cells

et al. 2020

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Cellular reprogramming forcing the expression of pluripotency markers can reverse aging of cells, but how molecular mechanisms through which reprogrammed cells alter aging-related cellular activities still remains largely unclear. In this study, we reprogrammed human synovial fluid-derived mesenchymal stem cells (MSCs) into induced pluripotent stem cells (iPSCs) using six reprogramming factors and reverted the iPSCs back to MSCs, as an approach to cell rejuvenation. Using the parental and reprogrammed MSCs as control nonrejuvenated and rejuvenated cells, respectively, for comparative analysis, we found that aging-related activities were greatly reduced in reprogrammed MSCs compared with those in their parental lines, indicating reversal of cell aging. Global transcriptome analysis revealed differences in activities of regulatory networks associated with inflammation and proliferation. Mechanistically, we demonstrated that, compared with control cells, the expression of GATA binding protein 6 (GATA6) in reprogrammed cells was attenuated, resulting in an increase in the activity of sonic hedgehog signaling and the expression level of downstream forkhead box P1 (FOXP1), in turn ameliorating cellular hallmarks of aging. Lower levels of GATA6 expression were also found in cells harvested from younger mice or lower passage cultures. Our findings suggest that GATA6 is a critical regulator increased in aged MSCs that controls the downstream sonic hedgehog signaling and FOXP1 pathway to modulate cellular senescence and aging-related activities.

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“…While the Hh pathway is critical for follicular morphogenesis in embryonic development and adult regeneration, there have been no studies comparing Shh expression in young and old mice during WIHN. However, age-related decrease Shh expression has been observed in other systems including endometrium where decreased Shh levels lead to impaired endometrial stem cell activity and poor endometrial renewal ( Cho et al, 2019 ). Interestingly, in HFSCs isolated from hair follicle bulges in young and old human scalp biopsies, Hh pathway genes were expressed at similar levels ( Rittie et al, 2009 ).…”

Section: Signaling Pathwaysmentioning

confidence: 99%

Wound Induced Hair Neogenesis – A Novel Paradigm for Studying Regeneration and Aging

Bhoopalam

Garza

Reddy

2020

Front. Cell Dev. Biol.

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Hair follicles are the signature dermal appendage of mammals. They can be thought of as mini-organs with defined polarity, distinct constituent cell types, dedicated neurovascular supply, and specific stem cell compartments. Strikingly, some mammals show a capacity for adult hair follicle regeneration in a phenomenon known as wound-induced hair neogenesis (WIHN). In WIHN functional hair follicles reemerge during healing of large cutaneous wounds, and they can be counted to provide an index of regeneration. While age-related decline in hair follicle number and cycling are widely appreciated in normal physiology, it is less clear whether hair follicle regeneration also diminishes with age. WIHN provides an extraordinary quantitative system to address questions of mammalian regeneration and aging. Here we review cellular and molecular underpinnings of WIHN, explore known age-related changes to these elements, and present unanswered questions for future exploration.

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An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2

Cited by 32 publications

References 48 publications

ATF3 drives senescence by reconstructing accessible chromatin profiles

ATF3 drives senescence by reconstructing accessible chromatin profiles

GATA6 regulates aging of human mesenchymal stem/stromal cells

Wound Induced Hair Neogenesis – A Novel Paradigm for Studying Regeneration and Aging

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