Lab Mission & Open Science
The Lian Lab aims to utilize stem cell differentiation, genome/epigenome editing techniques to convert human pluripotent stem cells (hPSCs) into fully functional somatic cells. The objective of the Lian lab is to develop stem cell therapies for Type 1 diabetes and cardiovascular diseases.
We are committed to openly sharing our tools and knowledge because open science is a key value of the Lian Lab.
The Lian lab distributes all the plasmids via Addgene, including our popular PiggyBac vector (XLone) for inducible gene expression in mammalian cells, as well as chemically modified mRNA (modRNA)-based gene editing constructs like Cas9 and ABE8e modRNA vectors. You can access all of these plasmids on our Addgene page: https://www.addgene.org/Xiaojun_Lian/
Genome/Epigenome Editing
Genome Editing: Our lab is working to develop universal donor stem cells for transplantation medicine applications via advanced genome editing technologies, including modRNA-based CRISPR (Cas9, Cas12) systems. You can access our modRNA paper here: https://www.cell.com/cell-reports-methods/pdf/S2667-2375(22)00172-2.pdf
Epigenome Editing: We have also developed modRNA-based epigenome editing tools (SAM and VPR systems) for direct programming of stem cell fate. Both SAM and VPR systems can activate endogenous target gene expression robustly when delivered with modRNA into human cells.
Cardiac Differentiation of Human Pluripotent Stem Cells (GiWi protocol)
We are implementing a variety of techniques, including small molecule mediated hPSC differentiation and direct programming, to efficiently generate cells of the cardiac lineages for regenerative medicine and therapeutic development.
We developed a groundbreaking approach for generating highly pure populations of cardiomyocytes from hPSCs through manipulation of a single developmental pathway (Wnt pathway) using only two small molecules, without the need for genetic selection or cell sorting. Our papers on small-molecule cardiomyocyte differentiation (published in PNAS and Nature Protocols) have been cited over 3,000 times, demonstrating widespread acceptance and recognition of our work.
You can access our paper here: Lian et al Nature Methods 2015; Lian et al PNAS 2012; Lian et al Nature Protocols 2013
Pancreatic Differentiation of Human Pluripotent Stem Cells
Our lab is using both directed differentiation and direct programming techniques to generate functional pancreatic beta cells from human pluripotent stem cells for treating type 1 diabetes.
Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) provide promising cell therapies for type 1 diabetes. Current PP differentiation requires a high amount of Activin A during the definitive endoderm (DE) stage, making it economically difficult for commercial ventures. Here we identify a dose-dependent role for Wnt signaling in controlling DE differentiation without Activin A. While high-level Wnt activation induces mesodermal formation, low-level Wnt activation by a small-molecule inhibitor of glycogen synthase kinase 3 is sufficient for DE differentiation, yielding SOX17+FOXA2+ DE cells. BMP inhibition further enhances this DE differentiation, generating over 87% DE cells. These DE cells could be further differentiated into PPs and functional β cells.
You can access our paper here: https://doi.org/10.1016/j.stemcr.2021.07.021
Time for experiments!
