A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells

Area of Science:

• Biomedical Research
• Stem Cell Biology
• Genetics

Background:

• Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder increasing risk for lung and liver disease.
• Patient-derived induced pluripotent stem cells (iPSCs) can model AATD, but limited lines exist.
• Phenotypic diversity in AATD necessitates a broader range of iPSC models.

Purpose of the Study:

• Establish and characterize a comprehensive repository of AATD patient iPSCs.
• Include associated clinical data to link genotype and phenotype.
• Provide a resource for AATD pathogenesis and therapeutic discovery.

Main Methods:

• Generated and curated a repository of AATD patient iPSCs.
• Collected and associated relevant clinical data with iPSC lines.
• Differentiated iPSCs into hepatic and lung cell lineages for functional analysis.
• Performed RNA sequencing on differentiated cell types.
• Utilized CRISPR/Cas9 gene editing for scarless repair in select iPSC lines.

Main Results:

• Established a curated repository of AATD iPSCs with diverse genetic backgrounds.
• Successfully differentiated iPSCs into hepatic and lung cell lineages.
• RNA sequencing provided insights into AATD-specific cellular mechanisms.
• Demonstrated the feasibility of genetic correction using CRISPR/Cas9.

Conclusions:

• The AATD iPSC repository offers a valuable tool for studying disease mechanisms.
• This resource facilitates the investigation of genotype-phenotype correlations in AATD.
• The repository supports the development and testing of novel therapeutic strategies for AATD.