Defining the competency of developing Mds1 (+) progenitors in Lung epithelial development

Authors: Mariadela Demoura, Laertis Ikonomou, Boris Kunnev

SUNY Campus: SUNY Buffalo

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 26

Timeslot: Session B 10:15-11:15 AM

Abstract: Mds1 is a transcription factor important to hematopoietic development, but little is known about its role in lung development. Using a conditional Mds1Cre mouse we will identify the competency of Mds1+ respiratory progenitors at early stages of lung development, such as embryonic and pseudoglandular. We used an Mds1Cre-ERT2x ROSA-loxp-STOP-loxp -YFP mouse strain to identify lineage-labeled progeny of Mds1(+) lung epithelial progenitors. Lungs were labeled at either E8.75 or E11.5 by tamoxifen administration using oral gavage. Mds1 labelled, paraffin-embedded lungs were analyzed at either E14.5 or E18.5. Immunohistochemistry staining techniques on the lineage-labelled lungs were used to identify various distinguishable markers of proximal and distal lung fate and their colocalization with the YFP trace. Stained lung sections were imaged using an epifluorescence microscope and image tiling. Results have indicated that use of an Mds1Cre mouse does show positive epithelial lineage tracing following tamoxifen pulse at E8.75 or E11.5. Distinct co-localization staining patterns for proteins related to embryonic lung epithelial development such as NKX2-1, EPCAM, SOX9, and YFP were seen in distinct anatomical areas of the lung such as the airways and distal tips. Interestingly, PAX8/YFP co-staining revealed the presence of Mds1(+) progenitors also in the developing thyroid gland. Our studies provide the first piece of evidence on the multipotency of early Mds1+ lung progenitors during embryonic development. Extended lineage tracing studies at alveolar and adult time points will be conducted to track developmental fates and will be combined with Mds1 RNA-scope staining to detect actual Mds1 expression at time points analyzed.