Yielding Ability and Stability and Adaptability of Proso Millet Varieties

The yielding ability and stability and adaptability of eight proso millet varieties from Shanxi,Inner Mongolia,Heilongjiang and Hebei were analyzed and evaluated in different ecological regions including Zhangjiakou,Huanghua and Shijiazhuang in 2015. The results showed that Chishu No. 2 and Jishu No. 2 have stronger yielding ability,and their grain yields were 3 144. 42( highest) and 3 133. 15 kg/ha respectively,ranking first and second in the test varieties. In areas with low fertility,especially in saline-alkali areas,they still have potential for high yields,so they are suitable for promotion in large areas in Hebei Province. Neimi No. 8 and Yanshu No. 11 showed special adaptability under different ecological conditions. They require high-fertility soil and can be planted in the spring millet area in north of Hebei.

A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological conditions.However,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive.Here,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response mechanisms.Through comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular regeneration.We found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic processes.Altogether,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration

Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice.We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1αin endothelial cells.Skin administration of a HIF-1αagonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que.Together,these findings provide a molecular understanding for the efficacy of Que in hair regrowth,which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine,and suggest a route of pharmacological intervention that may promote hair regrowth.

Chemical screen identifies a geroprotective role of quercetin in premature aging

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature aging.However,the pathogenesis of CS remains unclear due to the limitations of current disease models.Here,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 system.CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage stress.Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6.We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS pathologies.Moreover,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS.Collectively,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.

Low-dose quercetin positively regulates mouse healthspan

Dear Editor,Aging is the leading risk factor for many chronic diseases,accounting for almost 60%of all deaths worldwide.How to achieve healthy aging,alleviate aging-related diseases,and extend healthspan has become a main topic of biomedical research(He et al.,2019).Geroprotective compounds,such as metformin and rapamycin,have been shown to improve both healthspan and lifespan in mice(Martin-Montalvo et al.,2013;Bitto et al.,2016),whereas nicotinamide partially improves healthspan in mice(Mitchell et al.,2018).

Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells

Dear Editor,The interventions that slow aging or promote healthy aging may provide preventative measures for age-related diseases(Zhang et al.,2015).Therefore,it is crucial to identify drugs that target aging-related pathologies and improve health-span in geroscience research.Using model organisms such as C.elegans and rodents,several small molecules capable of alleviating the onset or progression of aging,including rapamycin,nicotinamide mononucleotide,and metformin,have been discovered(Partridge et al.,2020).However,the safety and efficacy of these chemicals still need in-depth evaluation before clinical applications(Partridge et al.,2020).As a result,it is necessary to identify additional compounds with geroprotective effects for human cells to counteract the general trend of populational aging.However,transforming a promising compound into an approved drug requires enormous resources.Alternatively,repurposing previously approved drugs for new clinical applications offers a more efficient and less costly path toward drug develop-ment.Therefore,testing U.S.Food and Drug Administration(FDA)-approved drugs for geroprotective effects may dis-covernew therapeutics that have already been stringently tested in humans for safety.

Low-dose chloroquine treatment extends the lifespan of aged rats

Dear Editor,Chloroquine(CQ)has long been used as an anti-malarial agent(Wellems and Plowe,2001).Recently,CQ has also been applied to treat viral infection and related diseases(Wellems and Plowe,2001;Huang et al.,2020).However,the safety and efficacy of its applications are still under extensive debate(Solomon and Lee,2009).Here,we discovered that low-dose CQ has a geroprotective effect on physiologically aged rats.Low-dose CQ prolonged lifespan,repressed systemic inflammation,and inhibited fibrosis across multiple tissue types in aged rats.Furthermore,we constructed transcriptomic maps for 6 tissues(kidney,small intestine,liver,heart,lung,and aorta)upon CQ treatment,thus revealing the effects of CQ at a systemic level.CQ treatment mitigated age-related molecular changes and repressed genes linked to fibrosis and the inflammatory response.Altogether,our data provide a valuable resource for investigating the impact of CQ on multiple aged tissues,which may facilitate the development of clinical applications that mitigate age-related changes in the elderly.

mTORC2/RICTOR exerts differential levels of metabolic control in human embryonic,mesenchymal and neural stem cells

Dear Editor,Stem cells,including pluripotent stem cells and adult stem cells,possess the remarkable capability of being able to selfrenew while at the same time having potential to differentiate into different cell lineages and functionally distinct cell types.Human embryonic stem cells(hESCs)can differentiate into all adult stem cell types,including human mesenchymal stem cells(hMSCs)and human neural stem cells(hNSCs),but can also give rise to all terminally differentiated cell types(Wang et al.,2021a).Through the continuous replenishment of differentiated cells,stem cells support tissue homeostasis and respond to tissue injuries.Given the promising applications of stem cells in cell therapy and regenerative medicine,insights into molecular events underlying stem cell maintenance,self-renewal ability and pluripotency,continue to garner strong interest(Shan et al.,2021).Although metabolic pathways have been implicated in the reciprocal regulations of stem cell self-renewal and differentiation as well as organ homeostatic maintenance(Garcia-Prat et al.,2017),central aspects of how metabolic requirements differ and are regulated across the various types of human stem cells in our body remain enigmatic.

Correction to:Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-019-0623-2 In Fig.7C,we used the ERCC6mut.iPSCs(CS iPSCs)as NANOG positive control pluripotent cells in the upper pan-els.However,these cells were inadvertently labeled as ERCC6^(GC)-iPSCs.In the revised version of Fig.7C,we have updated the high-quality images along with the corrected mark.In addition,we have also made corresponding chan-ges in the figure legend.