Редактирование: CDKN1C

Cyclin-dependent kinase inhibitor 1C (Cyclin-dependent kinase inhibitor p57) (p57Kip2) [KIP2]

==Publications==

{{medline-entry
|title=Human iPSC-derived [[MSC]]s (i[[MSC]]s) from aged individuals acquire a rejuvenation signature.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30885246
|abstract=Primary mesenchymal stem cells ([[MSC]]s) are fraught with aging-related shortfalls. Human-induced pluripotent stem cell (iPSC)-derived [[MSC]]s (i[[MSC]]s) have been shown to be a useful clinically relevant source of [[MSC]]s that circumvent these aging-associated drawbacks. To date, the extent of the retention of aging-hallmarks in i[[MSC]]s differentiated from iPSCs derived from elderly donors remains unclear. Fetal femur-derived [[MSC]]s (f[[MSC]]s) and adult bone marrow [[MSC]]s (a[[MSC]]s) were isolated, corresponding iPSCs were generated, and i[[MSC]]s were differentiated from f[[MSC]]-iPSCs, from a[[MSC]]-iPSCs, and from human embryonic stem cells (ESCs) H1. In addition, typical [[MSC]] characterization such as cell surface marker expression, differentiation capacity, secretome profile, and trancriptome analysis were conducted for the three distinct i[[MSC]] preparations-f[[MSC]]-i[[MSC]]s, a[[MSC]]-i[[MSC]]s, and ESC-i[[MSC]]s. To verify these results, previously published data sets were used, and also, additional a[[MSC]]s and i[[MSC]]s were analyzed. f[[MSC]]s and a[[MSC]]s both express the typical [[MSC]] cell surface markers and can be differentiated into osteogenic, adipogenic, and chondrogenic lineages in vitro. However, the transcriptome analysis revealed overlapping and distinct gene expression patterns and showed that f[[MSC]]s express more genes in common with ESCs than with a[[MSC]]s. f[[MSC]]-i[[MSC]]s, a[[MSC]]-i[[MSC]]s, and ESC-i[[MSC]]s met the criteria set out for [[MSC]]s. Dendrogram analyses confirmed that the transcriptomes of all i[[MSC]]s clustered together with the parental [[MSC]]s and separated from the [[MSC]]-iPSCs and ESCs. i[[MSC]]s irrespective of donor age and cell type acquired a rejuvenation-associated gene signature, specifically, the expression of [[INHBE]], [[DNMT3B]], POU5F1P1, [[CDKN1C]], and [[GCNT2]] which are also expressed in pluripotent stem cells (iPSCs and ESC) but not in the parental a[[MSC]]s. i[[MSC]]s expressed more genes in common with f[[MSC]]s than with a[[MSC]]s. Independent real-time PCR comparing a[[MSC]]s, f[[MSC]]s, and i[[MSC]]s confirmed the differential expression of the rejuvenation (COX7A, EZA2, and TMEM119) and aging (CXADR and IGSF3) signatures. Importantly, in terms of regenerative medicine, i[[MSC]]s acquired a secretome (e.g., angiogenin, DKK-1, IL-8, PDGF-AA, osteopontin, [[SERPINE1]], and VEGF) similar to that of f[[MSC]]s and a[[MSC]]s, thus highlighting their ability to act via paracrine signaling. i[[MSC]]s irrespective of donor age and cell source acquire a rejuvenation gene signature. The i[[MSC]] concept could allow circumventing the drawbacks associated with the use of adult [[MSC]]s und thus provide a promising tool for use in various clinical settings in the future.
|mesh-terms=* Aged
* Aging
* Antigens, Differentiation
* Cell Differentiation
* Female
* Fetus
* Humans
* Induced Pluripotent Stem Cells
* Male
* Mesenchymal Stem Cells
* Middle Aged
* Transcriptome
|keywords=* Aged MSC
* Aging
* Fetal MSCs
* Rejuvenation
* Secretome
* Transcriptome
* iMSCs
* iPSCs
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423778
}}
{{medline-entry
|title=Expansion of adipose tissue-derived stromal cells at "physiologic" hypoxia attenuates replicative senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28589682
|abstract=Multipotent mesenchymal stromal cells are considered as a perspective tool in cell therapy and regenerative medicine. Unfortunately, autologous cell therapy does not always provide positive outcomes in elder donors, perhaps as a result of the alterations of stem cell compartments. The mechanisms of stem and progenitor cell senescence and the factors engaged are investigated intensively. In present paper, we elucidated the effects of tissue-related O  on morphology, functions, and transcriptomic profile of adipose tissue-derived stromal cells (ASCs) in replicative senescence in vitro model. Replicatively senescent ASCs at ambient (20%) O  (12-21 passages) demonstrated an increased average cell size, granularity, reactive oxygen species level, including anion superoxide, lysosomal compartment activity, and IL-6 production. Decreased ASC viability and proliferation, as well as the change of more than 10 senescence-associated gene expression were detected (IGF1, [[CDKN1C]], [[ID1]], [[CCND1]], etc). Long-term ASC expansion at low O  (5%) revoked in part the replicative senescence-associated alterations.
|mesh-terms=* Adipose Tissue
* Cell Culture Techniques
* Cell Hypoxia
* Cells, Cultured
* Cellular Senescence
* Female
* Gene Expression Regulation
* Humans
* Male
* Mesenchymal Stem Cells
|keywords=* ASCs
* ROS
* functional state of organelles
* hypoxia
* paracrine activity
* senescence
* senescence-associated genes
|full-text-url=https://sci-hub.do/10.1002/cbf.3267
}}