A functional genomics approach to investigate the differentiation of iPSCs into lung epithelium at air-liquid interface.

Journal of Cellular and Molecular Medicine
Jenny L KerschnerAnn Harris

Abstract

The availability of robust protocols to differentiate induced pluripotent stem cells (iPSCs) into many human cell lineages has transformed research into the origins of human disease. The efficacy of differentiating iPSCs into specific cellular models is influenced by many factors including both intrinsic and extrinsic features. Among the most challenging models is the generation of human bronchial epithelium at air-liquid interface (HBE-ALI), which is the gold standard for many studies of respiratory diseases including cystic fibrosis. Here, we perform open chromatin mapping by ATAC-seq and transcriptomics by RNA-seq in parallel, to define the functional genomics of key stages of the iPSC to HBE-ALI differentiation. Within open chromatin peaks, the overrepresented motifs include the architectural protein CTCF at all stages, while motifs for the FOXA pioneer and GATA factor families are seen more often at early stages, and those regulating key airway epithelial functions, such as EHF, are limited to later stages. The RNA-seq data illustrate dynamic pathways during the iPSC to HBE-ALI differentiation, and also the marked functional divergence of different iPSC lines at the ALI stages of differentiation. Moreover, a comparison of ...Continue Reading

References

May 1, 1988·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·M J WhitcuttR Wu
May 26, 1999·American Journal of Respiratory Cell and Molecular Biology·D W BorthwickJ R Dorin
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·K Chan, Y W Kan
Aug 23, 2002·Seminars in Cancer Biology·Elena M KlenovaVictor V Lobanenkov
Jun 5, 2003·Nature Reviews. Cancer·Raghu Kalluri
Jun 24, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yingjian YouSteven L Brody
Jan 26, 2005·The Journal of Biological Chemistry·Huajing WanJeffrey A Whitsett
Jan 24, 2007·Physiological Reviews·Yutaka MaedaJeffrey A Whitsett
Mar 31, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·David E MetzgerJohn M Shannon
Nov 22, 2007·Science·Junying YuJames A Thomson
Jul 5, 2008·Development·Huajing WanJeffrey A Whitsett
Jan 22, 2010·Nature·Thomas BeckerMichael Hoch
Jul 2, 2010·Current Opinion in Genetics & Development·Klaus H Kaestner
Jan 20, 2011·Genes & Development·Adrian Kee Keong TeoLudovic Vallier
May 7, 2011·Methods in Molecular Biology·Scott H RandellJohn C Olsen
Nov 8, 2011·Genes & Development·Kenneth S Zaret, Jason S Carroll
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frederik SeilerChristoph Beisswenger
Sep 28, 2013·Nature Protocols·Qi WangDieter Weichenhan
Oct 19, 2013·The Journal of Clinical Investigation·Mahboobe GhaediLaura E Niklason
Nov 23, 2013·Nature Protocols·Su WangX Shirley Liu
Dec 3, 2013·Nature Biotechnology·Sarah X L HuangHans-Willem Snoeck
Mar 20, 2014·Journal of Cellular Biochemistry·Scott A Rankin, Aaron M Zorn
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Amy L FirthInder M Verma
Apr 18, 2014·Proceedings of the National Academy of Sciences of the United States of America·Brigitte N Gomperts
Aug 28, 2014·Journal of Cellular Physiology·Laertis Ikonomou, Darrell N Kotton
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 7, 2015·Current Protocols in Molecular Biology·Jason D BuenrostroWilliam J Greenleaf
Feb 6, 2015·Nature Protocols·Sarah X L HuangHans-Willem Snoeck
Feb 20, 2015·Nature·Alexander M TsankovAlexander Meissner
Sep 6, 2015·European Journal of Cell Biology·Zhen-Yu She, Wan-Xi Yang
Jan 26, 2016·Molecular and Cellular Endocrinology·James A BrowneAnn Harris

❮ Previous
Next ❯

Citations

Jan 3, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jenny L KerschnerAnn Harris
Jan 22, 2021·Molecular and Cellular Endocrinology·James A BrowneAnn Harris
Jul 31, 2021·Scientific Reports·Nadzeya MarozkinaBenjamin Gaston

❮ Previous
Next ❯

Datasets Mentioned

BETA
GTX101507
GSE97036

Methods Mentioned

BETA
Assay
FACS
PCR
PCA

Software Mentioned

HOMER
Cuffdiff
Cufflinks
featureCounts
Subread
Integrated Genomics Viewer ( IGV )
gProfiler
DESeq2
UCSC browser
Subread package

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.