Poster Presentation ASSCR, AGCTS, ISCT ANZ and Friends Joint Scientific Conference 2019

Molecular & functional characterisation of human induced trophoblast stem cells derived from fibroblasts. (#137)

Xiaodong Liu* 1 2 , Kathryn C Davidson* 1 2 , Daniela S Valdes 1 2 , Jia Tan 1 2 , Jan Schroeder 1 2 , John F Ouyang 3 , Owen Rackham 3 , Jose M Polo 1 2
  1. Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia
  2. Department of Anatomy & Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  3. Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore

Trophoblast cells play an imperative role in embryonic development, as they establish the interface between mother and foetus through placentation. Human trophoblast stem cells (TSCs) were long unable to be derived in vitro and have been recently established from human blastocysts and first-trimester placentas. Importantly, we have been able to generate for the first time induced trophoblast stem cells (iTSCs) that in all aspects tested thus far are indistinguishable from primary human TSCs. iTSCs express TSC markers: GATA2/3, KRT7, TFAP2C, TEAD4, TP63, APA & ITGA6, secrete hCG, and exhibit transcriptional profiles that cluster with primary TSCs from blastocyst/placenta. They have been cultured for >50 passages in our lab without any change in phenotype or senescence. Furthermore, they undergo directed bi-potential differentiation into ST and EVT cells, a fundamental characteristic of TSCs. iTSC-ST cells express SDC1 and CGB, secrete hCG, and fuse to form multinucleated cells. iTSC-EVT cells express HLA-G and MMP-2. Our iTSCs also differentiate in vivo to secrete hCG in mouse lesion assays. Ultimately, our data strongly suggests that our lines are comparable to human TSCs and are generated entirely from somatic cells via transcription factor-mediated cell fate transition, thus avoiding the need for human embryos or prenatal tissue use. This provides an easily accessible and longevous source of cells for implantation and placental studies; and postulates a missing link for understanding early human embryogenesis, that until now has largely relied almost entirely on pluripotent stem cells (PSCs) in isolation and without extra-embryonic tissue interactions with TSCs.

  • Have you presented your abstract at another international meeting?: No