Inflammation and aging:signaling pathways and intervention therapies

Aging is characterized by systemic chronic inflammation,which is accompanied by cellular senescence,immunosenescence,organ dysfunction,and age-related diseases.Given the multidimensional complexity of aging,there is an urgent need for a systematic organization of inflammaging through dimensionality reduction.

Generating hematopoietic cells from human pluripotent stem cells:approaches,progress and challenges

Human pluripotent stem cells(hPSCs)have been suggested as a potential source for the production of blood cells for clinical application.In two decades,almost all types of blood cells can be successfully generated from hPSCs through various differentiated strategies.Meanwhile,with a deeper understanding of hematopoiesis,higher efficiency of generating progenitors and precursors of blood cells from hPSCs is achieved.However,how to generate large-scale mature functional cells from hPSCs for clinical use is still difficult.In this review,we summarized recent approaches that generated both hematopoietic stem cells and mature lineage cells from hPSCs,and remarked their efficiency and mechanisms in producing mature functional cells.We also discussed the major challenges in hPSC-derived products of blood cells and provided some potential solutions.Our review summarized efficient,simple,and defined methodologies for developing good manufacturing practice standards for hPSC-derived blood cells,which will facilitate the translation of these products into the clinic.

Correction:Generating hematopoietic cells from human pluripotent stem cells:approaches,progress and challenges

Correction:Cell Regen 12,31(2023).https://doi.org/10.1186/s13619-023-00175-6 Following publication of the original article(Zheng et al.2023),the authors reported that Figs.1 and 2 were in the wrong order.The correct Figs.1 and 2 have been provided in this Correction.The original article(Zheng et al.2023)has been corrected.

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune diseases.Particularly,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ dysfunction.However,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the host.Although a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear.In the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS.Considering that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

Correction:Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Since the publication of this review1,the authors noticed one inadvertent mistake occurred in Fig.6c that needs to be corrected.The correct Fig.6 is provided as follows.In detail,"Human-derived CAR-T cells"has been replaced by"Mouse-derived CAR-T cells"in the revised fig.6c.The key findings of the article are not affected by these corrections.The original review article has been corrected.

Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steady-state blood using a polypeptide-forming 3D culture

Although widely applied in treating hematopoietic malignancies,transplantation of hematopoietic stem/progenitor cells(HSPCs)is impeded by HSPC shortage.Whether circulating HSPCs(cHSPCs)in steady-state blood could be used as an alternative source remains largely elusive.Here we develop a three-dimensional culture system(3DCS)including arginine,glycine,aspartate,and a series of factors.Fourteen-day culture of peripheral blood mononuclear cells(PBMNCs)in 3DCS led to 125-and 70-fold increase of the frequency and number of CD34+cells.Further,3DCS-expanded cHSPCs exhibited the similar reconstitution rate com-pared to CD34+HSPCs in bone marrow.Mechanistically,3DCS fabricated an immunomodulatory niche,secreting cytokines as TNF to support cHSPC survival and proliferation.Finally,3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization.Our 3DCS successfully expands rare cHSPCs,providing an alternative source for the HSPC therapy,particularly for the patients/donors who have failed in HSPC mobilization.

Epigenetic regulation of hematopoietic stem cell homeostasis

As one of the best characterized adult stem cells,hematopoietic stem cell(HSC)homeostasis is of great importance to hematopoiesis and immunity due to HSC’s abilities of self-renewal and multi-lineage differentiation into functional blood cells.However,excessive self-renewal of HSCs can lead to severe hematopoietic malignancies like leukemia,whereas deficient selfrenewal of HSCs may result in HSC exhaustion and eventually apoptosis of specialized cells,giving rise to abnormalities such as immunodeficiency or anemia.How HSC homeostasis is maintained has been studied for decades and regulatory factors can be generally categorized into two classes:genetic factors and epigenetic factors.Although genetic factors such as signaling pathways or transcription factors have been well explored,recent studies have emerged the indispensable roles of epigenetic factors.In this review,we have summarized regulatory mechanisms of HSC homeostasis by epigenetic factors,including DNA methylation,histone modification,chromatin remodeling,non-coding RNAs,and RNA modification,which will facilitate applications such as HSC ex vivo expansion and exploration of novel therapeutic approaches for many hematological diseases.

Single-cell RNA-seq technology lends a hand into HSC ontogeny

Hematopoietic stem cells（HSCs）are rare populations in the bone marrow of adult mammals which produce millions of blood cells for daily circulation by balancing self-renewal and multi-lineage differentiation.In vertebrates,a subset of

SARS-CoV-2 N protein potentiates host NPM1-snoRNA translation machinery to enhance viral replication

Dear Editor,COVID-19(Coronavirus Disease 2019)is causing an unprecedented public health crisis.Protein translation is crucial for virus lifecycle.Nucleocapsid(N)protein is among the most abundant SARS-CoV-2 proteins and highly conserved across coronavirus genus.1 However,its function in subverting host translation machinery is still elusive.

Small noncoding RNAs play superior roles in maintaining hematopoietic stem cell homeostasis

The maintenance of the mammalian blood system depends on hematopoietic stem cells(HSCs),which are a rare class of adult stem cells with self-renewal and multilineage differentiation capacities.The homeostasis of hematopoietic stem cells is finely tuned by a variety of endogenous and exogenous regulatory factors,and disrupted balance will lead to hematological diseases including leukemia and anemia.Recently,emerging studies have illustrated the cellular and molecular mechanisms underlying the regulation of HSC homeostasis.Particularly,the rapid development of second-generation sequencing technologies has uncovered that many small noncoding RNAs(ncRNAs)are highly expressed in HSCs,including snoRNAs,miRNAs,tsRNAs,circular RNAs,etc.In this study,we will summarize the essential roles and regulatory mechanisms of these small ncRNAs in maintaining HSC homeostasis.Overall,this review provides up-to-date information in the regulation of HSC homeostasis by small ncRNAs,which sheds light into the development of therapeutic strategies against hematopoietic malignancies.