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Single cell transcriptomic profiling provides insight into maturational and developmental status of pluripotent stem cell-derived erythroblasts

ABSTRACT: Single cell transcriptomic profiling provides insight into maturational and developmental status of pluripotent stem cell-derived erythroblasts

PROVIDER: PRJNA438561 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6845540.fastq.gz	Fastqsanger.gz
	SRR6845550.fastq.gz	Fastqsanger.gz
	SRR6845560.fastq.gz	Fastqsanger.gz
	SRR6845570.fastq.gz	Fastqsanger.gz
	SRR6845580.fastq.gz	Fastqsanger.gz

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Single cell transcriptomic profiling provides insight into maturational and developmental status of pluripotent stem cell-derived erythroblasts

Project description:Robust β-globin expression in erythroid cells derived from induced pluripotent stem cells (iPSCs) would increase the resolution with which red blood cell disorders such as sickle cell disease and β thalassemia can be modeled in vitro. To better quantify efforts in augmenting β-globin expression, we report the creation of a β-globin reporter iPSC line through the insertion of a GFP cassette after the endogenous β-globin promoter, allowing for the mapping of β-globin expression throughout erythroid development in real time at single cell resolution. Sorting live GFP+ and GFP- cells at the most mature stage of erythroid differentiation, followed by single cell RNA sequencing (scRNAseq), identifies features that distinguish GFP- from GFP+ β-globin expressing cells and allows for the dissection of the developmental and maturational status of iPSC-derived erythroid cells. Co-expression of embryonic, fetal and adult globins in individual cells indicates a yolk sac erythro-myeloid progenitor (EMP) stage of hematopoietic development, representing the onset of definitive erythropoiesis. Within this developmental program, scRNAseq analysis identifies a gradient of erythroid maturation with GFP+ β-globin expressing cells showing increased maturation. In addition, scRNAseq analysis reveals that definitively patterned iPSC-derived erythroblasts resemble their postnatal counterparts in terms of gene expression and essential biological processes, confirming their potential for disease modeling and regenerative medicine applications.

2018-07-31 | GSE111860 | GEO

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