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Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy [ChIP-seq]

ABSTRACT: Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy [ChIP-seq]

PROVIDER: PRJNA661026 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12569860_1.fastq.gz	Fastqsanger.gz
	SRR12569860_2.fastq.gz	Fastqsanger.gz
	SRR12569861_1.fastq.gz	Fastqsanger.gz
	SRR12569861_2.fastq.gz	Fastqsanger.gz
	SRR12569862_1.fastq.gz	Fastqsanger.gz

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Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy

Project description:Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy

| PRJNA661195 | ENA

Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy [Array]

Project description:Personalized cell therapy is being explored as promising treatments for incurable diseases such as Parkinson’s disease (PD). Here, we directly reprogrammed human fibroblasts into induced dopaminergic neuronal progenitors (hiDPs) and assess their applicability for regenerative PD therapy. We found that hiDPs maintain progenitor characteristics over 20 passages and showed unaltered differentiation potential to midbrain dopaminergic neurons. By next-generation sequencing, we confirm that even long-term cultured hiDPs retain genomic stability, resulting in absence of tumorigenicity when transplanted, indicating preclinical safety. The hiDPs differentiate into highly pure dopaminergic neurons expressing markers associated with positive graft outcomes without unwanted serotonergic neurons known to cause graft-induced dyskinesia. The therapeutic effect and safety were confirmed by transplantation in rodent PD models. Because our optimized reprogramming conditions generate highly expandable hiDPs enabling scaled production of clonal cells and overcoming quality control issues, we propose that our hiDPs can become a preferred autologous therapy for aged and feeble PD patients vulnerable to immunosuppression regimens.

2023-08-31 | GSE157392 | GEO

Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy [ChIP-seq]

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Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy [Array]

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Enrichment, proteome analysis and transplantation of human embryonic stem cell derived dopaminergic progenitors expressing LMX1a

Project description:Despite the progress in safety and efficacy of cell therapy with pluripotent stem cells (PSCs), the presence of residual undifferentiated stem cells or proliferating neural progenitor cells (NPCs) with rostral identity has remained a major challenge. Here we reported the generation of an LMX1A knock-in GFP reporter human embryonic stem cell (hESC) line that marks the early dopaminergic progenitors during neural differentiation. Purified GFP positive cells in vitro exhibited expression of mRNA and proteins that characterized and matched the midbrain dopaminergic identity. Further proteomic analysis of enriched LMX1A+ cells identified several membrane associated proteins including CNTN2, enabling prospective isolation of LMX1A+ progenitor cells. Transplantation of hPSC-derived purified CNTN2+ progenitors enhanced dopamine release from transplanted cells in the host brain and alleviated Parkinson’s disease symptoms in animal models. Our study establishes an efficient approach for purification of large numbers of hPSC-derived dopaminergic progenitors for therapeutic applications.

2018-06-06 | PXD007837 | Pride

Isolation of human iPSC-derived dopaminergic progenitors by cell sorting

Project description:Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells may inevitably contain tumorigenic or inappropriate cells. Purification of neural progenitor cells or DA neurons as suitable donor cells has been attempted, but the isolation of DA progenitor cells derived from human pluripotent stem cells has so far been unsuccessful. Here we show human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, Corin. we were able to develop a method for 1) scalable DA neuron induction on human laminin fragment and 2) sorting DA progenitor cells using an anti-Corin antibody. Furthermore, we determined the optimal timing for the cell sorting and transplantation. The grafted cells survived well and functioned as midbrain DA neurons in the 6-OHDA-lesioned rats, and showed minimal risk of tumor formation. The sorting of Corin-positive cells is favorable in terms of both safety and efficiency, and our protocol will contribute to the clinical application of human iPSCs for Parkinson’s disease. Differentiated human iPSC-derived neural progenitors just after sorting (day12 unsorted, day12 Corin+) and dopaminergic progenitors after an aggregation culture (day28 and day42, unsorted and day12-sorted, respectively), and human fetal ventral mesencephalon and dorsal mesencephalon (gestational age of 7.5 weeks) were subjected to RNA extraction and hybrdization on Affymetrix microarrays. Each sample except for human mesencephalon, undifferentiated iPSC, and day12-unsorted, day42-sample has 3 or 4 repeats.

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Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson’s disease. [scRNA-Seq]

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Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-31 | GSE157394 | GEO