Speaker

Jinsong Li

Time

2025.03.05 16:00-17:30

Abstract

From mouse androgenetic haploid blastocysts derived by injection of sperm into enucleated oocytes, we generated androgenetic haploid embryonic stem cells (AG-haESCs) that can support full-term embryonic development upon injection into oocytes, leading to the production of semi-cloned (SC) mice (semi-cloning technology). However, one major drawback of this technology is the very low birth rate of healthy SC mice (2% of total SC embryos transferred). Recently, we established AG-haESCs carrying H19-DMR and IG-DMR deletions (DKO-AG-haESCs) that can efficiently support the generation of SC pups at a rate of 20% (“sperm-like stem cell”). Meanwhile, through optimizing the derivation and culture conditions, we have obtained sperm-like stem cells with intact H19 and IG-DMR methylations that can further improve the birth rate of SC pups at an efficiency of 30%. Moreover, we established haploid ESCs from monkey and human parthenogenetic embryos and most recently human sperm-like stem cells from androgenetic embryos. Sperm-like stem cell-mediated SC technology, combined with CRISPR-Cas9 technologies, enables one-step generation of mouse models that mimic the dosage reduction of multiple genes in human Myotonic Dystrophy type 1 (DM1); identification of novel mutations involved in human neural tube defects; medium-scale targeted screening of critical factors involved in bone development; base mutagenesis of a specific protein-coding gene to identify critical amino acids for protein function in vivo; efficient generation of mice carrying tagged proteins at genome-scale (Genome Tagging Project, GTP); and creation of mouse models with 19 pairs of chromosomes. In summary, sperm-like stem cells provide powerful tools for genetic analyses in mammals at the organismal level.

Bio

Dr. Li obtained his PhD degree from Institute of Zoology, Chinese Academy of Sciences followed by postdoctoral training at Rockefeller University before joining Shanghai Institute of Biochemistry and Cell Biology in 2007. His research mainly focuses on stem cells and embryonic development. He has made fundamental contributions to the establishment of androgenetic haploid embryonic stem cells (also termed sperm-like stem cells or artificial spermatids) that can be used as sperm replacement for efficient production of semi-cloned mice (so called SC technology). Li has made great efforts to promote the applications of SC technology and shown that it can be used for complex genetic analyses in mice, including efficient generation of mouse models carrying defined point mutations related to human developmental defects; one-step generation mouse models that mimic multiple genetic defects in diseases; and targeted screening of critical genes or nucleotides of a specific gene involved in a developmental process. Recently, Li initiated a project to tag every protein in mice based on SC technology (genome tagging project, GTP), which may enable the precise description of protein atlas in mice.