Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
Transposable elements(TEs)have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes.Acute myeloid leukemia(AML)develops as a consequence of a series of genetic c...Transposable elements(TEs)have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes.Acute myeloid leukemia(AML)develops as a consequence of a series of genetic changes in hematopoietic precursor cells,including mutations in epigenetic factors.Here,we set out to study the gene regulatory role of TEs in AML.We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data.We show that a large number of TEs in general,and more specifically mammalian-wide interspersed repeats(MIRs),are more enriched in AML cells than in normal blood cells.We obtained a similar finding when analyzing histone modification data in AML patients.Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis.To functionally validate their regulatory role,we selected 19 MIR regions in AML cells,and tested them for enhancer activity in an AML cell line(Kasumi-1)and a chronic myeloid leukemia(CML)cell line(K562);the results revealed several MIRs to be functional enhancers.Taken together,our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.展开更多
Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades.
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+14 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA141)the Science and Technology Major Project of Hunan Provincial Science and Technology Department(2021SK1010)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Natural Science Foundation of Sichuan Province(2023NSFSC0003)Yunnan Fundamental Research Project(202201AS070080)the State Key Laboratory of Membrane Biology。
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金supported by grants from the National Natural Science Foundation of China(91749205,91329302,and 31210103916)Ministry of Science and Technology of China(2015CB964803 and 2016YFE0108700)+2 种基金a Max Planck fellowship to J.D.J.H.supported by the National Human Genome Research Institute(NHGRI)and the National Cancer Institute(1R01CA197139)NHGRI(1UM1HG009408)the National Health Lung and Blood Institute(1R01HL138424)。
文摘Transposable elements(TEs)have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes.Acute myeloid leukemia(AML)develops as a consequence of a series of genetic changes in hematopoietic precursor cells,including mutations in epigenetic factors.Here,we set out to study the gene regulatory role of TEs in AML.We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data.We show that a large number of TEs in general,and more specifically mammalian-wide interspersed repeats(MIRs),are more enriched in AML cells than in normal blood cells.We obtained a similar finding when analyzing histone modification data in AML patients.Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis.To functionally validate their regulatory role,we selected 19 MIR regions in AML cells,and tested them for enhancer activity in an AML cell line(Kasumi-1)and a chronic myeloid leukemia(CML)cell line(K562);the results revealed several MIRs to be functional enhancers.Taken together,our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.
文摘Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades.
