Identifying Global Rejuvenation Mechanisms in Tissues that Reverses Age-Related Phenotypes in Planarians
openNIA - National Institute on Aging
PROJECT SUMMARY/ABSTRACT
The preservation of organ functions, such as eyesight and mobility, is a significant health concern in the elderly
population. Organ frailty and disease progression are associated with the dysregulation of tissue homeostasis,
which is typically regulated by regenerative units, consisting of adult stem cells (ASCs) and neighboring niche
cells that regulate ASC function. Therefore, to better understand why regenerative functions decrease in aged
individuals, uncovering how aging alters niche cell types and expression (mRNA) is critical for discovering
regenerative therapeutical approaches.
The potential to uncover molecular mechanisms to reverse age-related disorders prompted me to spatially
profile microenvironmental niches in young, old, and regenerated tissues. I have recently developed Ex-Scope,
which integrates Expansion Microscopy and Seq-Scope, a submicrometer-resolution ST (spatial
transcriptomic) technology, to obtain a high-resolution multi-Omic method that represents an order of
magnitude improvements over Seq-Scope. With the assistance of Dr. Guo, who has extensively worked on
planarian tissues, we optimized Ex-Scope to spatially profile planarian tissue. Planarians are capable of
regenerating any lost body part, but most importantly, regenerated tissues have a youthful tissue architecture;
thus, making them ideal to study tissue homeostasis and rejuvenation. Using mRNA single-cell data on young,
old, and regenerated planarians, as a reference dataset (obtained by Dr. Guo), we will provide spatial insight
into rejuvenating mechanisms between microenvironmental niches and stem cells. Concurrent, we will
demonstrate the advantageous resolution of Ex-Scope by profiling RNA granules in planarian stem cells and
oocytes (young, old, and regenerated), which are compartmentalized biomolecules that regulate transcription
in stem cells and the establishment of pluripotency. In aim 1) we propose to characterize RNA granules and
soluble transcriptomes in planarian stem cells and oocytes, with a hypothesis that the granular structures in
oocytes and ASCs would have transcriptome contents distinct from soluble cytoplasm, and 2) we propose to
profile microenvironmental niches and their changes during aging and rejuvenation, with a hypothesis that
aging and rejuvenation will affect cellular (single cell), tissue-level (microenvironment) and subcellular level
(RNA granule) transcriptome, each of which is important for tissue function and homeostasis. We expect that
the current work will give us a systematic understanding of how aging deteriorates tissue function by altering
transcriptomic structure at both microscopic and macroscopic levels, and how regeneration can reverse it and
rejuvenate tissue homeostasis.
Up to $44K
health research