JC Nat Biotech 24 (3)

Nat Biotech 24 (3) March 2006 content

Pyle AD, LF Lock, PJ Donovan. (2006) Neurotrophins mediate human embryonic stem cell survival. Nat Biotech 24 (3): 344-350

Many growth factors promote growth or self-renewal of human Embryonic Stem Cells (hESC), including FGF2, BMP antagonist Noggins, and ones involved in Wnt/ -catenin and activin/TGF . Micro-array and SAGE data/screening suggest tropomyosin-related kinase (TRK) receptors present in hESC, and may contribute to the growth or self-renewal of hESC.

Peter Donovan group found TRK receptors were indeed expressed and functional in hESC. The ligands of those receptors, namely neurotrophins, promote colonal survival of hESC and also retain the pluri/multi-potency of hESC. While inhibition of those receptors function results in hESC apoptosis. Signal transduction analyses suggest neutrophins induce phosphorylation of TRK receptors through PI3K, but not MAPK pathway. The findings may help high throughput screening for important factors of hESC growth and differentiation, under influence of neutrophins.

Interestingly, PTEN of PI3K pathway has been proved important in maintenance of stem cell renewal ability, and may be involved in various tumorigenesis processes.
Paper of interest:

Chao MV. (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4 (4): 299-309

Patapoutian A, LF Reichardt. (2001) Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 11 (3): 272-80

Richards M, SP Tan, JH Tan, WK Chan, A Bongso. (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22 (1): 51-64

Sato N, IM Sanjuan, M Heke, M Uchida, F Naef, AH Brivanlou. (2003) Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 260 (2): 404-13

Herszfeld D, E Wolvetang, E Langton-Bunker, T-L Chung, AA Filipczyk, S Houssami, P Jamshidi, K Koh, AL Laslett, A Michalska, L Nguyen, BE Reubinoff, I Tellis, JM Auerbach, CJ Ording, LHJ Looijenga, MF Pera. (2006) CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotech 24 (3): 351-357

Genetic instabilities or cytogenetic abnormalities in hESC are acquired during in vitro propagation, and may contribute to the tumorigenesis in human. Cytogenetics was almost the only method used for the examination of those abnormalities. Martin Pera group recently identified CD30, a member of TNF receptor superfamily, presented in transformed hESC, but not normal ones. Expression of CD30 protects hESC from apoptosis.