Xiaofei Li

My research explores the mechanisms underlying neurodevelopment and regeneration, with a particular focus on the molecular regulation of neural stem and progenitor cells throughout life span and after injury in the central nervous system (CNS). My primary research goal is to leverage the knowledge of developmental and stem cell biology for regenerative medicine. Using cutting-edge technologies, such as single-cell and spatial omics, advanced computational algorithms, human organoids, and gene editing, I aim to elucidate the molecular and cellular dynamics of stem cells, translating these insights into therapeutic strategies for CNS injuries. Recently, I have expanded my work to include the developmental origins of neurological diseases and CNS cancers, establishing a robust framework for addressing these conditions. We have established extensive collaborations with various research groups in Sweden, France, UK, China, and USA. 

My ongoing research comprises three main directions with a strong focus on human stem cell biology:

1) Stem Cells and Development: To investiagte stem cell subtypes that give rise to disctinct neural subpopulations through unique regulations in the human developing CNS, and to leverage this knowledge to develop new stem cell therapies for precise cell fate control in CNS injuries.

In this research line, we have revealed the heterogeneity of different neural cells, including neural stem cells in the developing human brain and spinal cord. However, as of today, a general challenge is that single-cell and spatial omics cannot fully distinguish “subtype” and “transient cell state”, due to the dynamics of cell and molecular changes during development. We are now utilizing high-resolution spatial transcriptomics on early developmental human CNS, and developing new bioinformatic pipelines to identify spatially organized stem cell subtypes. The results will be further translated for CNS injury treatments in the future in combination with genetic pertubation. 

2) Stem Cells and Aging: To elucidate how human neural stem and progenitor cells lose their regenerative potential during maturation and aging, and how to rejuvenate the aged CNS.

One key challenge to regenerate the damage CNS is due to the loss of stem cell properties during maturation and aging of the human body. It is controvesial that whether human neural stem cells in the adulthood can be reactivated, or even whether they still exist in the adult human CNS. We are now identifying whether or not human neural stem cells exist throughout the life span, and the key genetic and epigenetic regulations that drive human stem cells to be quiescent. 

3) Stem Cells and Disease Origin: To reveal the origin of CNS diseases and novel treatments

Beyond the development and regeneration studies, I have set up two new research lines in my lab since 2022, focusing on the origin of CNS diseases, including pediatric brain tumor (ependymomas) and Alzheimer’s disease (AD). My previous study has shown that cancer stem cells in ependymomas recapitulate neurodevelopment (Li et al., Nature Neuroscience, 2023), revealing potential molecular signatures as potential targets for tumor origin without interfering normal developing brain. We are now using single-cell and spatial omics on human ependymomas, and correlated these molecular mechanisms to patient survival and tumor recurrence. Moreover, we are also investiagting whether age-related neurodegenerative diseases may also have a developmental origin. We are using different genetically modified animal models and human patient-derived organoid for this study.