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Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells [ATAC-Seq]

ABSTRACT: Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells [ATAC-Seq]

PROVIDER: PRJNA1082201 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28162591_1.fastq.gz	Fastqsanger.gz
	SRR28162591_2.fastq.gz	Fastqsanger.gz
	SRR28162592_1.fastq.gz	Fastqsanger.gz
	SRR28162592_2.fastq.gz	Fastqsanger.gz
	SRR28162593_1.fastq.gz	Fastqsanger.gz

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Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells [scRNA-seq]

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Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells [ATAC-Seq]

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Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells [RNA-Seq]

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Project description:Unraveling complex signaling programs animating developmental lineage-decisions is pivotal to differentiate human pluripotent stem cells (hPSC) into pure populations of desired lineages for regenerative medicine. Developmental signals are strikingly temporally dynamic: BMP and Wnt initially specify primitive streak (progenitor to endoderm) yet 24 hours later suppress endoderm and induce mesoderm. At lineage bifurcations we show mutually-exclusive embryonic lineages are segregated through cross-repressive signals: TGFM-NM-2 and BMP/MAPK duel to respectively specify pancreas versus liver from endoderm. Unilateral endodermal differentiation requires blockade of alternative fates at every stage, revealing a universal developmental strategy for efficient differentiation and anterior-posterior patterning of diverse hPSC lines into highly-pure endodermal populations. This culminated in hPSC-derived hepatic progenitors that, for the first time, engraft long-term in genetically-unconditioned mouse livers and secrete human albumin. Finally, thirty transcriptional and chromatin state maps capturing endoderm commitment revealed endodermal enhancers reside in an unanticipated diversity of "pre-enhancer" chromatin states before activation. Endoderm RNA-seq and ChIP-seq data sets

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