دورية أكاديمية
أعرض في EDS

Multi-omic rejuvenation of human cells by maturation phase transient reprogramming.

التفاصيل البيبلوغرافية
العنوان: Multi-omic rejuvenation of human cells by maturation phase transient reprogramming.
المؤلفون: Gill D; Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom., Parry A; Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom., Santos F; Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom., Okkenhaug H; Imaging Facility, Babraham Institute, Cambridge, United Kingdom., Todd CD; Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom., Hernando-Herraez I; Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom., Stubbs TM; Chronomics Limited, London, United Kingdom., Milagre I; Laboratory for Epigenetic Mechanisms/Chromosome Dynamics Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal., Reik W; Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.; Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom.
المصدر: ELife [Elife] 2022 Apr 08; Vol. 11. Date of Electronic Publication: 2022 Apr 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Induced Pluripotent Stem Cells* , Rejuvenation*, Cellular Reprogramming/genetics ; DNA Methylation ; Epigenome ; Epigenomics/methods ; Fibroblasts ; Humans ; Middle Aged
مستخلص: Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of somatic cell reprogramming, which suggests full reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first "maturation phase transient reprogramming" (MPTR) method, where reprogramming factors are selectively expressed until this rejuvenation point then withdrawn. Applying MPTR to dermal fibroblasts from middle-aged donors, we found that cells temporarily lose and then reacquire their fibroblast identity, possibly as a result of epigenetic memory at enhancers and/or persistent expression of some fibroblast genes. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome was rejuvenated to a similar extent, including H3K9me3 levels and the DNA methylation ageing clock. The magnitude of rejuvenation instigated by MPTR appears substantially greater than that achieved in previous transient reprogramming protocols. In addition, MPTR fibroblasts produced youthful levels of collagen proteins, and showed partial functional rejuvenation of their migration speed. Finally, our work suggests that optimal time windows exist for rejuvenating the transcriptome and the epigenome. Overall, we demonstrate that it is possible to separate rejuvenation from complete pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.
Competing Interests: DG, AP, FS, HO, CT, IH, IM No competing interests declared, TS is CEO and shareholder of Chronomics, WR is a consultant and shareholder of Cambridge Epigenetix. Is employed by Altos Labs
(© 2022, Gill et al.)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; 210754/Z/18/Z United Kingdom WT_ Wellcome Trust; 215912/Z/19/Z United Kingdom WT_ Wellcome Trust; United Kingdom BB_ Biotechnology and Biological Sciences Research Council
فهرسة مساهمة: Keywords: DNA methylation; ageing; genetics; genomics; human; regenerative medicine; rejuvenation; reprogramming; stem cells; transcription
سلسلة جزيئية: GEO GSE165180; GSE113957; GSE107654; GSE54848; GSE110544
تواريخ الأحداث: Date Created: 20220407 Date Completed: 20220425 Latest Revision: 20240216
رمز التحديث: 20240216
مُعرف محوري في PubMed: PMC9023058
DOI: 10.7554/eLife.71624
PMID: 35390271
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.71624