Development of
sensory organs
in organoids
Learning about how sensory placodes arise using the pluripotent stem cell-derived organoid system.
Over the past 15 years, stem cell-derived organoid research has grown steadily, yet few models for sensory systems exist. While extensively working and optimizing the inner ear organoid system during my postdoctoral research project, I 1) recognized that 3D organoid systems could serve as powerful tools for addressing mammalian peripheral sensory (including inner ear) biology questions and 2) developed a strong interest in early inner ear development in mammals, a topic that is not amenable to traditional techniques. I am particularly focused on the early development of cranial sensory placodes, which later give rise to a variety of sensory organs (including the inner ear), using stem cell-derived 3D organoid systems.
Illustration of sensory placodes in ~E10.5 mouse embryo
Organoid on a chip
I started a collaboration with the bioengineer, Dr. Ashutosh Agarwal, in the University of Miami a while ago and our project focuses on the development of an innovated microfluidic chip that exhibits molecular gradients in a high volume space where the organoid is subject to. The system will allow us to mimic morphogen gradients and test their impacts on cell differentiation and cell fate determination. The study is recently funded by the American Hearing Research Foundation.
We published our study focusing on 1) elucidating the molecular mechanisms underlying Wnt-mediated induction and posteriorization of the PPE (a critical step for the development of the otic placode), 2) uncovering the origin of the PPE, and 3) improving inner ear organoid productivity and reproducibility.
My postdoctoral research project was focused on modeling the genetic basis of hair cell degeneration using mouse embryonic stem cell (mESC)-derived inner ear organoids, and I have generated several mESC-derived organoid lines carrying mutations in a hearing loss-related gene, Tmprss3. We have incorporated many cutting-edge techniques aside from 3D organoid culture, including CRISPR/Cas9 assay and scRNA-Seq, and our results have revealed that inner ear organoids recapitulate pathological phenotypes in vivo; this means that inner ear organoids can be used to study genetic-associated mutations (Tang et al. 2019). In addition, I have worked tightly with Dr. Karl Koehler’s group and was involved in a breakthrough study on hair follicles in mESC-derived skin organoids (Lee et al. 2018).
My Ph.D. research aimed to uncover the molecular and cellular processes of hair bundle repair in the model sea anemone Nematostella vectensis. First, I elucidated the dynamic nature of cadherin-23, a critical component of tip links, in hair bundles of sea anemones (Tang and Watson, 2014). Secondly, I identified secreted proteins that are involved in hair cell repair and regeneration. Our data suggested that these proteins, which are possibly secreted via exosomes, aid in re-connecting tip links between stereocilia that had been severed by trauma exposure (Tang and Watson, 2015). Furthermore, I applied the findings in a mammalian system (the mouse) and found, intriguingly, positive effects of anemone proteins on mammalian hair cell repair (Tang et al., 2016). This Journal of Experimental Biology article gathered quite a bit of media press and was considered a “highlighted” article (Inside JEB) and featured in Proto Magazine.
