Holloway, E. M. | Search bioRxiv

bioRxiv2018

Developing Future Biologists: creating and assessing a portable short course to engage underrepresented undergraduate students in developmental biology

Many barriers discourage underrepresented students from pursuing science careers. To access graduate education, undergraduate students must first gain exposure to a particular subject and subsequently accumulate related coursework and research experience. Many underrepresented students lack exposure to developmental biology due to limited undergraduate course offerings and finite resources at smaller institutions. To address this disparity, a group of University of Michigan graduate students and postdoctoral fellows created a portable short course focusing on developmental biology, titled \"Developing Future Biologists\" (DFB). This weeklong educational initiative provides hands-on laboratory sessions, interactive lectures, and professional development workshops to teach students about developmental biology and increase awareness of scientific career options. To evaluate course effectiveness, we developed a pre-post assessment, incorporating main ideas from the BioCore Guide. Student understanding of basic concepts and perceived experience in developmental biology increased in DFB participants, despite the abbreviated nature of the course. Here, we provide all course materials and an in-depth analysis of the assessment we created. The DFB portable short course model is an easily adaptable tool that connects undergraduate students with opportunities for advanced study and lowers barriers for underrepresented students in science, technology, engineering, and mathematics.

scientific communication and education↗

bioRxiv2018

Basal stem cell fate specification is mediated by SMAD signaling in the developing human lung

Basal stem cells (basal cells), located in the bronchi and trachea of the human lung epithelium, play a critical role in normal airway homeostasis and repair, and have been implicated in the development of diseases such as cancer1-4. Additionally, basal-like cells contribute to alveolar regeneration and fibrosis following severe injury5-8. However, the developmental origin of basal cells in humans is unclear. Previous work has shown that specialized progenitor cells exist at the tips of epithelial tubes during lung branching morphogenesis, and in mice, give rise to all alveolar and airway lineages9,10. These bud tip progenitor cells have also been described in the developing human lung11-13, but the mechanisms controlling bud tip differentiation into specific cell lineages, including basal cells, are unknown. Here, we interrogated the bud tip-to-basal cell transition using human tissue specimens, bud tip progenitor organoid cultures11, and single-cell transcriptomics. We used single-cell mRNA sequencing (scRNAseq) of developing human lung specimens from 15-21 weeks gestation to identify molecular signatures and cell states in the developing human airway epithelium. We then inferred differentiation trajectories during bud tip-to-airway differentiation, which revealed a previously undescribed transitional cell state ( hub progenitors) and implicated SMAD signaling as a regulator of the bud tip-to-basal cell transition. We used bud tip progenitor organoids to show that TGFT1 and BMP4 mediated SMAD signaling robustly induced the transition into functional basal-like cells, and these in vitro-derived basal cells exhibited clonal expansion, self-renewal and multilineage differentiation. This work provides a framework for deducing and validating key regulators of cell fate decisions using single cell transcriptomics and human organoid models. Further, the identification of SMAD signaling as a critical regulator of newly born basal cells in the lung may have implications for regenerative medicine, basal cell development in other organs, and understanding basal cell misregulation in disease.

developmental biology↗