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Comparison of adult stem cells of various human donors

ABSTRACT: Comparison of adult stem cells of various human donors

PROVIDER: PRJNA867007 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20946852_1.fastq.gz	Fastqsanger.gz
	SRR20946852_2.fastq.gz	Fastqsanger.gz
	SRR20946853_1.fastq.gz	Fastqsanger.gz
	SRR20946853_2.fastq.gz	Fastqsanger.gz
	SRR20946854_1.fastq.gz	Fastqsanger.gz

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Comparison of adult stem cells of various human donors

Project description:We would like to check differences among stem cells derived from various donors. The purpose of this project is to investigate donor dependency for stem cell implantation.

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Comparison of epithelial cells from various epithelia and hair follicle stem cells

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Comparison of epithelial cells from various epithelia and hair follicle stem cells [microarray]

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Comparison of epithelial cells from various epithelia and hair follicle stem cells

Project description:The potency of an adult stem cell is restricted to certain lineages during embryonic life, in response to a specific microenvironment (the niche) and it is maintained for life. Lineage restriction is considered immutable. We have investigated if adult stem cells isolated from different epithelia could change fate by exposing them to a hairy skin niche. We have demonstrated that clonogenic stem cells restricted to a single epithelial lineage and cultured from various Tp63-expressing tissues e.g, the bladder, the vagina, or the thymus can acquire new functionality. When exposed to a hair skin microenvironment, these stem cells acquire the capacity to generate hair follicles and sebaceous glands, thus behaving like bona fide hairy skin multipotent stem cells. Genome wide-screen analysis has demonstrated that the stem cells express transcription factors typical of hair follicle differentiation, even though they continue to express some of the genes linked to their origin. This increase in potency demonstrates that lineage restriction is not immutable.

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Metformin Ingestion Rejuvenates Myoblasts from Older Adult Donors

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Comparison of epithelial cells from various epithelia and hair follicle stem cells [microarray]

Project description:The potency of an adult stem cell is restricted to certain lineages during embryonic life, in response to a specific microenvironment (the niche) and it is maintained for life. Lineage restriction is considered immutable. We have investigated if adult stem cells isolated from different epithelia could change fate by exposing them to a hairy skin niche. We have demonstrated that clonogenic stem cells restricted to a single epithelial lineage and cultured from various Tp63-expressing tissues e.g, the bladder the oral mucous, the oesophagus or the thymus can acquire new functionality. When exposed to a hair skin microenvironment, these stem cells acquire the capacity to generate hair follicles and sebaceous glands, thus behaving like bona fide hairy skin multipotent stem cells. Genome wide-screen analysis has demonstrated that the stem cells express transcription factors typical of hair follicle differentiation, even though they continue to express some of the genes linked to their origin. This increase in potency demonstrates that lineage restriction is not immutable.

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Tissue-specific mutation accumulation in human adult stem cells during life

Project description:Gradual accumulation of mutations in human adult stem cells during life is associated with various age-related diseases, including cancer. The number of stem cell divisions throughout life is believed to be a major determinant for mutation accumulation and could explain the extreme variation of cancer incidence across different organs. Yet, mutation patterns and rates of healthy adult stem cells remain unknown. Here, we determined genome-wide mutation patterns in primary adult stem cells of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years. We find that the number of mutations increases linearly with age up to several thousand mutations per cell at 87 years of age, while mutation spectra remain constant throughout life. Small intestine and colon stem cells have a 2-fold higher mutation rate per year compared with liver stem cells. These differences could be exclusively attributed to the mutagenic action of spontaneous deamination of cytosine residues and may reflect the high stem cell division rate in these tissues. The genomic distribution of somatic mutations is non-random and predominantly associated with DNA replication dynamics in the small intestine and colon, and with transcription in the liver. These results indicate that a stable balance between various mutagenic and DNA repair processes is maintained throughout life and that the activity of these processes in adult stem cells varies between tissues.

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Project description:Adult stem cell-based therapeutic approaches have great potential in regenerative medicine because of their immunoregulatory properties and multidifferentiation capacity. Nevertheless, the outcomes of stem cell‑based therapies to date have shown inconsistent efficacy owing to donor variation, thwarting the expectation of clinical effects. However, such donor dependency has been elucidated by biological consequences that current research could not predict. Here, we introduce cellular morphology-based prediction to determine the multipotency rate of human nasal turbinate stem cells (hNTSCs), aiming to predict the differentiation rate of keratocyte progenitors. We characterized the overall genes and morphologies of hNTSCs from five donors and compared stemness-related properties, including multipotency and specific lineages, using mRNA sequencing. It was demonstrated that transformation factors affecting the principal components were highly related to cell morphology. We then performed a convolutional neural network-based analysis, which enabled us to assess the multipotency level of each cell group based on their morphologies with 85.98% accuracy. Surprisingly, the trend in expression levels after ex vivo differentiation matched well with the deep learning prediction. These results suggest that AI‑assisted cellular behavioral prediction can be utilized to perform quantitative, non-invasive, single-cell, and multimarker characterizations of live stem cells for improved quality control in clinical cell therapies.

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Comparison of gene expression profiles by CD3+CD4+ thymocytes derived from fetal and adult hematopoietic stem cells

Project description:Human fetal and adult hematopoietic stem cells (HSC) were obtained from fetal liver, fetal bone marrow (BM), and adult BM. These were injected into human fetal thymic implants in SCID-hu Thy/Liv mice (4-6 separate mice per HSC donor) and allowed to mature into single positive CD4+ (SP4) thymocytes over the course of 7-8 weeks. SP4 thymocytes from injected stem cells were subsequently sort-purified from thymic implants and gene expression was performed. HSC from fetal (age 18-22 gestational weeks) and adult (age: 19-43 year old) HLA-A2+ donors were obtained from different tissues. After injection into human fetal thymic implants (SCID-hu Thy/Liv HLA-A2-) the cells were allowed to mature into thymocytes and sorted on the basis of HLA-A2+ expression and CD3+CD4+ (SP4) expression. 3 separate thymic implants were analyzed for each group.

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