Identifying global rejuvenation mechanisms in tissues that reverses age-related phenotypes in planarians

The National Institute on Aging awarded the Regents of the University of Michigan $131,842 on February 22, 2026, under the Aging Research program (CFDA 93.866, Assistance Listing Project Grant F31AG094300).

The recipient will use the funding to identify global rejuvenation mechanisms in tissues that reverse age-related phenotypes in planarians. The research involves developing and optimizing EX-SCOPE, a high-resolution spatial transcriptomic technology that integrates expansion microscopy and SEQ-SCOPE to profile microenvironmental niches in young, old, and regenerated planarian tissues at submicrometer resolution. The investigator will use mRNA single-cell reference data, obtained in collaboration with Dr. Guo, to provide spatial insight into rejuvenating mechanisms between microenvironmental niches and stem cells. The work will also profile RNA granules in planarian stem cells and oocytes to examine how aging alters niche cell types and expression, with the goal of uncovering molecular mechanisms that could reverse age-related disorders and preserve organ functions such as eyesight and mobility in elderly populations.

The University of Michigan, operating through its Office of Research and Sponsored Projects Division, serves as the recipient. Performance will take place in Ann Arbor, Michigan, with a period of performance ending August 31, 2028.

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.