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Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation

ABSTRACT: Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation

PROVIDER: PRJNA545622 | ENA |

REPOSITORIES: ENA

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Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation

Project description:Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSCs, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-lymphocytes and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited the expected hypertrophic phenotype. Whole genome sequencing (WGS) based annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modeling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.

2019-10-03 | GSE132012 | GEO

Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation

Project description:Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSC, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-cells and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited a hypertrophic phenotype as expected. WGS annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modelling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.

| EGAS00001003684 | EGA

4f4844f2-52a2-44d1-bb37-e12fd73cf525 - samples

Project description:This is 2nd part of data for original Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation,

| EGAD00001005359 | EGA

Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation Committee

Project description:Data Access Committee EGAC00001001226

| EGAC00001001226 | EGA

Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation Committee (part II)

Project description:Data Access Committee EGAC00001001332

| EGAC00001001332 | EGA

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A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues

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