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Putative role of hyaluronan and its related genes, HAS2 and RHAMM, in human early preimplantation embryogenesis and embryonic stem cell characterization

Lookup NU author(s): Dr Meenakshi Choudhary, Petra Stojkovic, Dr Louise Hyslop, Dr George Anyfantis, Professor Mary Herbert, Professor Alison Murdoch, Professor Miodrag Stojkovic, Professor Majlinda LakoORCiD


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Human embryonic stem cells (hESC) promise tremendous potential as a developmental and cell therapeutic tool. The combined effort of stimulatory and inhibitory signals regulating gene expression, which drives the tissue differentiation and morphogenetic processes during early embryogenesis, is still very poorly understood. With the scarcity of availability of human embryos for research, hESC can be used as an alternative source to study the early human embryogenesis. Hyaluronan (HA), a simple hydrating sugar, is present abundantly in the female reproductive tract during fertilization, embryo growth, and implantation and plays an important role in early development of the mammalian embryo. HA and its binding protein RHAMM regulate various cellular and hydrodynamic processes from cell migration, proliferation, and signaling to regulation of gene expression, cell differentiation, morphogenesis, and metastasis via both extracellular and intracellular pathways. In this study, we show for the first time that HA synthase gene HAS2 and its binding receptor RHAMM are differentially expressed during all stages of preimplantation human embryos and hESC. RHAMM expression is significantly downregulated during differentiation of hESC, in contrast to HAS2, which is significantly upregulated. Most importantly, RHAMM knockdown results in downregulation of several pluripotency markers in hESC, induction of early extraembryonic lineages, loss of cell viability, and changes in hESC cycle. These data therefore highlight an important role for RHAMM in maintenance of hESC pluripotency, viability, and cell cycle control. Interestingly, HAS2 knockdown results in suppression of hESC differentiation without affecting hESC pluripotency. This suggests an intrinsic role for HAS2 in hESC differentiation process. In accordance with this, addition of exogenous HA to the differentiation medium enhances hESC differentiation to mesodermal and cardiac lineages. ©AlphaMed Press.

Publication metadata

Author(s): Choudhary M, Zhang X, Stojkovic P, Hyslop L, Anyfantis G, Herbert M, Murdoch AP, Stojkovic M, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2007

Volume: 25

Issue: 12

Pages: 3045-3057

Print publication date: 01/12/2007

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.


DOI: 10.1634/stemcells.2007-0296

PubMed id: 17872502


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Funder referenceFunder name
BBS/B/14779Biotechnology and Biological Sciences Research Council
BB/E012841/1Biotechnology and Biological Sciences Research Council
G0300486Medical Research Council
G0301182Medical Research Council