Pub Date : 2025-01-02DOI: 10.1038/s41422-024-01057-5
Yuting Wang, Wenhao Zhang, Chao Zhang, Hoang Q. Tran Van, Takashi Seino, Yi Zhang
Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150low HSCs from old mice but not their CD150high counterparts can effectively differentiate into downstream lineage cells. Notably, transplantation of old CD150low HSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150high HSCs. Importantly, reducing the dysfunctional CD150high HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and that aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.
{"title":"Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice","authors":"Yuting Wang, Wenhao Zhang, Chao Zhang, Hoang Q. Tran Van, Takashi Seino, Yi Zhang","doi":"10.1038/s41422-024-01057-5","DOIUrl":"10.1038/s41422-024-01057-5","url":null,"abstract":"Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150low HSCs from old mice but not their CD150high counterparts can effectively differentiate into downstream lineage cells. Notably, transplantation of old CD150low HSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150high HSCs. Importantly, reducing the dysfunctional CD150high HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and that aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"45-58"},"PeriodicalIF":28.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01057-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-02DOI: 10.1038/s41422-024-01016-0
Wenyu Fu, Meng Chen, Kaidi Wang, Yujianan Chen, Yazhou Cui, Yangli Xie, Zi-Ning Lei, Wenhuo Hu, Guodong Sun, Guiwu Huang, Chaopeng He, Jackie Fretz, Aubryanna Hettinghouse, Ronghan Liu, Xianyi Cai, Mingshuang Zhang, Yuehong Chen, Nan Jiang, Minchun He, Daniel H. Wiznia, Huiyun Xu, Zhe-Sheng Chen, Lin Chen, Kanglai Tang, Hong Zhou, Chuan-Ju Liu
Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO. Tau deficiency largely abolished bone loss induced by high-dose dexamethasone, a synthetic GC, in both inflammatory arthritis and GIO models. Furthermore, TRx0237, a Tau inhibitor identified from an FDA-approved drug library, effectively prevented GIO. Notably, combinatorial administration of TRx0237 and dexamethasone completely overcame the osteoporosis adverse effect of dexamethasone in treating inflammatory arthritis. These findings present Tau as a previously unrecognized GC receptor with low affinity, and provide potential strategies to mitigate a spectrum of GC-related adverse effects, particularly osteoporosis.
{"title":"Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss","authors":"Wenyu Fu, Meng Chen, Kaidi Wang, Yujianan Chen, Yazhou Cui, Yangli Xie, Zi-Ning Lei, Wenhuo Hu, Guodong Sun, Guiwu Huang, Chaopeng He, Jackie Fretz, Aubryanna Hettinghouse, Ronghan Liu, Xianyi Cai, Mingshuang Zhang, Yuehong Chen, Nan Jiang, Minchun He, Daniel H. Wiznia, Huiyun Xu, Zhe-Sheng Chen, Lin Chen, Kanglai Tang, Hong Zhou, Chuan-Ju Liu","doi":"10.1038/s41422-024-01016-0","DOIUrl":"10.1038/s41422-024-01016-0","url":null,"abstract":"Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO. Tau deficiency largely abolished bone loss induced by high-dose dexamethasone, a synthetic GC, in both inflammatory arthritis and GIO models. Furthermore, TRx0237, a Tau inhibitor identified from an FDA-approved drug library, effectively prevented GIO. Notably, combinatorial administration of TRx0237 and dexamethasone completely overcame the osteoporosis adverse effect of dexamethasone in treating inflammatory arthritis. These findings present Tau as a previously unrecognized GC receptor with low affinity, and provide potential strategies to mitigate a spectrum of GC-related adverse effects, particularly osteoporosis.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"23-44"},"PeriodicalIF":28.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01016-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-23DOI: 10.1038/s41422-024-01066-4
Sofiya Zbaranska, Sheena A. Josselyn
During learning experience, a subset of astrocytes in the hippocampus is activated and becomes both necessary and sufficient for subsequent memory recall. Williamson et al. discovered that these learning-associated astrocytes play an important role in memory by modulating engram neurons’ synaptic activity and facilitating the reactivation of engram neuron ensembles during memory retrieval.
{"title":"Astrocytes: emerging stars of engrams","authors":"Sofiya Zbaranska, Sheena A. Josselyn","doi":"10.1038/s41422-024-01066-4","DOIUrl":"https://doi.org/10.1038/s41422-024-01066-4","url":null,"abstract":"<p><b>During learning experience, a subset of astrocytes in the hippocampus is activated and becomes both necessary and sufficient for subsequent memory recall. Williamson et al. discovered that these learning-associated astrocytes play an important role in memory by modulating engram neurons’ synaptic activity and facilitating the reactivation of engram neuron ensembles during memory retrieval</b>.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"113 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-20DOI: 10.1038/s41422-024-01065-5
Niels Niethard, Jan Born
In a recent work published inNature, Wang et al. reveal how protein kinase A and calcineurin dynamically regulate the daily duration of sleep and wake periods at excitatory post-synapses in the brain. This study uncovers key molecular mechanisms offering new insights into the enzymatic control of sleep homeostasis.
{"title":"Tug of war between phosphatase and kinase during sleep","authors":"Niels Niethard, Jan Born","doi":"10.1038/s41422-024-01065-5","DOIUrl":"https://doi.org/10.1038/s41422-024-01065-5","url":null,"abstract":"<p><b>In a recent work published in</b> <b><i>Nature</i></b><b>, Wang et al. reveal how protein kinase A and calcineurin dynamically regulate the daily duration of sleep and wake periods at excitatory post-synapses in the brain. This study uncovers key molecular mechanisms offering new insights into the enzymatic control of sleep homeostasis.</b></p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"10 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1038/s41422-024-01062-8
Cell Research Editorial Team
{"title":"Correction: Sanofi-Cell Research outstanding paper award of 2023","authors":"Cell Research Editorial Team","doi":"10.1038/s41422-024-01062-8","DOIUrl":"10.1038/s41422-024-01062-8","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"84-84"},"PeriodicalIF":28.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01062-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-06DOI: 10.1038/s41422-024-01053-9
Daolin Tang, Rui Kang, Guido Kroemer
Recent research published inSciencereveals that menadione, a precursor to vitamin K, induces a unique cell death pathway called triaptosis by oxidizing phosphatidylinositol 3-kinase PIK3C3/VPS34. This oxidation leads to endosomal dysfunction, highlighting how excessive oxidative stress can compromise cellular structures and activate specific cell death pathways.
{"title":"Triaptosis: an endosome-dependent cell death modality","authors":"Daolin Tang, Rui Kang, Guido Kroemer","doi":"10.1038/s41422-024-01053-9","DOIUrl":"https://doi.org/10.1038/s41422-024-01053-9","url":null,"abstract":"<p><b>Recent research published in</b> <b><i>Science</i></b> <b>reveals that menadione, a precursor to vitamin K, induces a unique cell death pathway called triaptosis by oxidizing phosphatidylinositol 3-kinase PIK3C3/VPS34. This oxidation leads to endosomal dysfunction, highlighting how excessive oxidative stress can compromise cellular structures and activate specific cell death pathways</b>.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"17 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-28DOI: 10.1038/s41422-024-01055-7
Pin Wang, Xiaoyu Hu
{"title":"Encoding immune responses: the moonlighting function of alanyl-tRNA synthetase.","authors":"Pin Wang, Xiaoyu Hu","doi":"10.1038/s41422-024-01055-7","DOIUrl":"https://doi.org/10.1038/s41422-024-01055-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：