Further analysis shows blocking apoptosis doesn’t extend the window of RGC neurogenesis, but delays their early neurogenesis and maturation. It also prolongs RGC lifespan and improves survival of mature RGCs. These results reveal more complex effects of apoptosis on RGC development than expected. /7
How does this affect RGCs? snRNA-seq and immunostaining show increased abundance of RGCs in BAX/BAK dKO organoids during their degeneration phase. Usually, RGCs gradually die out after 100 days of organoid culture, but in dKO organoids, we observed SNCG+ RBPMS+ RGCs at day 200! /6
To study the effects of retinal apoptosis on RGCs, we differentiated human BAX/BAK double-knockout (BAX/BAK dKO) organoids, in which apoptosis is abolished. Meanwhile, we observed increased necrosis in these organoids. /5
Interestingly, the early apoptotic wave during RGC generation causes loss of neurogenic retinal progenitors and newborn neuronal precursors, but not RGCs. These two apoptotic waves in organoids are reminiscent of programmed cell death seen in mammalian retinal development in vivo. /4
We developed a co-staining method to visualize apoptosis and necrosis in organoids carrying permanently GFP-labeled RGCs. We found two waves of apoptosis in retinal layers & one wave of necrosis specifically in the core. Late apoptosis and necrosis drive RGC loss over time. /3
Programmed cell death occurs during retinal development. In organoids, long-term RGC survival is limited, restricting their potential for therapeutic applications, but how this loss relates to cell death is unclear. We saw three phases for RGCs in organoids: generation, migration, degeneration /2
Excited to see my PhD work is now published @cp-cellreports.bsky.social ! In this study, we used human retinal organoids to investigate how cell death occurs and affects the development and survival of retinal ganglion cells (RGCs), the projection neurons in the eye /1 www.cell.com/cell-reports...
Many thanks to Brian, Clayton and @sethblackshaw.bsky.social for the computational analysis, Caterina, Meghana and Ya-Wen for the samples, and @bobbyjeyeguy.bsky.social for the mentorship and support throughout the journey. Thrilled to see what discoveries lie ahead! 👀
Excited to share my PhD work! We characterize waves of cell death during human retinal development, and show how blocking apoptosis promotes RGC long-term survival and alters their developmental dynamics in organoids. These findings will improve future organoid design for retinal disease modeling‼️
Our latest preprint is out, focusing on characterizing the response of Lhx6-positive neurons of the zona incerta (ZI) to naturally-occurring and experimentally-induced changes in the need to sleep, also known as sleep pressure.
www.biorxiv.org/content/10.1...
Check out this tour de force work from @christ3na.bsky.social in my lab!
Her studies reveal how developmental timing in the retina is controlled like an hourglass. The progenitor:neuron ratio shifts to control signaling levels and trigger photoreceptor development over time. Check it out!!
Happy for this paper to be out on direct circadian-independent effects of light on glucose and lipid metabolism. Spearheaded by student, Xiangning Chen, and in collaboration with Haiqing Zhao and @samerhattar.bsky.social
www.science.org/doi/10.1126/...
Wrapping up my first CSHL meeting #CSHL2024Brain ! Had a great time discussing and learning a lot from this welcoming and inspiring community💡Many thanks to organizers @sergiuppasca.bsky.social and Dr. Guo-li Ming for making this meeting fruitful and enjoyable to all attendees, especially trainees!
Heading out of town for the 2024 #cshlbrain meeting at Cold Spring Harbor Laboratory and ready to dive into the fascinating world of brain organoids!