Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Fast Chemical Reprogramming System to Generate Human Pluripotent Stem Cells

ABSTRACT: Chemical reprogramming enables the generation of human pluripotent stem cells (hCiPSCs) from somatic cells using small molecules, providing a novel and promising strategy for regenerative medicine. However, the current method for generating hCiPSCs is time consuming, and some cell lines from different donors are resistant to chemical induction, significantly limiting the utility of these cells for personalized medicine. Here, we developed a fast-reprogramming system capable of generating hCiPSCs in as few as 10 days. This accelerated method enables efficient generation of hCiPSCs with a consistent 100% success rate across 15 different donors. In particular, the efficiency of reprogramming within 16 days for cells refractory to previously reported protocols increased more than 30-fold. Mechanistically, we identified KAT3A/B and KAT6A as key epigenetic obstacles, as suppression of these factors facilitated the transition of somatic cells to a poised state by triggering switches in the epigenome, a process essential for this fast-reprogramming system. These results highlight the superiority of this novel system for generating hCiPSCs, which represents a next-generation approach for manufacturing cells for clinical applications. This work also advances our understanding of human cell reprogramming and paves the way for broader applications of chemical reprogramming in regenerative medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE264659 | GEO | 2024/10/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Fast Chemical Reprogramming System to Generate Human Pluripotent Stem Cells [RNA-seq]

Project description:Chemical reprogramming enables the generation of human pluripotent stem cells (hCiPSCs) from somatic cells using small molecules, providing a novel and promising strategy for regenerative medicine. However, the current method for generating hCiPSCs is time consuming, and some cell lines from different donors are resistant to chemical induction, significantly limiting the utility of these cells for personalized medicine. Here, we developed a fast-reprogramming system capable of generating hCiPSCs in as few as 10 days. This accelerated method enables efficient generation of hCiPSCs with a consistent 100% success rate across 15 different donors. In particular, the efficiency of reprogramming within 16 days for cells refractory to previously reported protocols increased more than 30-fold. Mechanistically, we identified KAT3A/B and KAT6A as key epigenetic obstacles, as suppression of these factors facilitated the transition of somatic cells to a poised state by triggering switches in the epigenome, a process essential for this fast-reprogramming system. These results highlight the superiority of this novel system for generating hCiPSCs, which represents a next-generation approach for manufacturing cells for clinical applications. This work also advances our understanding of human cell reprogramming and paves the way for broader applications of chemical reprogramming in regenerative medicine.

2024-10-27 | GSE264658 | GEO

CGH analyses of human induced pluripotent stem cells

Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications. Genomic instability induced by reprogramming or genetic modification would be a main issue for the safe use of these cells. We analyzed primary hIPSC lines and genetically modified derivatives by array-based comparative genomic hybridization.

2011-09-01 | E-MEXP-3316 | biostudies-arrayexpress

Genome-wide chromatin binding of Elk1 and Gli2 in chemical induced neural reprogramming

Project description:Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small molecule-driven approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging to develop. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine small molecules (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts towards a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study therefore provides an effective chemical approach for generating neural stem cells from mouse fibroblasts, and reveals mechanistic insights into underlying reprogramming process. Genome-wide binding of Elk1 and Gli2 was analyzed by CHIP-seq for tdMEFs from day 0 (ciNSLC), day 4 (D4), day 8 (D8) of M9-induced neural reprogramming, and ciNSLCs and pri-NPC.

2016-05-15 | E-GEOD-78976 | biostudies-arrayexpress

Genome-wide chromatin landscape of chemical-induced neural stem cell reprogramming from defined fibroblasts

Project description:Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small molecule-driven approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging to develop. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine small molecules (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts towards a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study therefore provides an effective chemical approach for generating neural stem cells from mouse fibroblasts, and reveals mechanistic insights into underlying reprogramming process. Genome-wide epigenetic changes of H3K4me1, H3K4me3, H3K27me3, and H3K27ac were analyzed by CHIP-seq for tdMEFs from day 0 (ciNSLC), day 4 (D4), day 8 (D8) of M9-induced neural reprogramming, and ciNSLCs and pri-NPC.

2016-05-15 | E-GEOD-78977 | biostudies-arrayexpress

Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins

Project description:To date, all methods to generate induced pluripotent stem (iPS) cells require the use of genetic materials and/or potentially mutagenic chemicals. Here we report the generation of stable human iPS cells from human fibroblasts by directly delivering defined reprogramming proteins. This system eliminates the potential risks associated with genetic and/or chemical manipulation, and could provide a safe and physiologically intact source of cells for regenerative medicine.

2009-05-29 | GSE16093 | GEO

SNP analysis of human induced pluripotent stem cells

Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications. We analyzed hiPSC line and genetically modified derivatives using high-density SNP array to investigate genomic instability associated reprogramming and genetic modification.

2011-09-01 | GSE31035 | GEO

Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming (CUT&TAG)

Project description:We recently demonstrated the chemical reprogramming of human somatic cells to pluripotent stem cells, which provides a fundamentally new approach for cell fate manipulation. However, the utility of this chemical approach is currently hampered by the slow kinetics. Here, by screening for new small-molecule boosters and systematically optimizing the original chemical reprogramming condition, we have established a robust, chemically defined protocol. With this new protocol, the entire chemical reprogramming process is remarkably accelerated, reducing the time needed from ~50 days to a minimum of 16 days. Moreover, this new protocol enables highly reproducible and efficient generation of human pluripotent stem cells from all 17 tested donors with a reprogramming efficiency of up to 31%. Our method provides a unique and powerful strategy for human cell fate manipulation and pluripotent stem cell manufacturing for cell-based therapeutic applications.

2023-04-26 | GSE230576 | GEO

Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming (RNA-Seq)

2023-04-26 | GSE213161 | GEO