Journal of Molecular Medicine

, Volume 86, Issue 8, pp 875–886 | Cite as

Deconstructing human embryonic stem cell cultures: niche regulation of self-renewal and pluripotency

  • Morag H. Stewart
  • Sean C. Bendall
  • Mickie BhatiaEmail author


The factors and signaling pathways controlling pluripotent human cell properties, both embryonic and induced, have not been fully investigated. Failure to account for functional heterogeneity within human embryonic stem cell (hESC) cultures has led to inconclusive results in previous work examining extrinsic influences governing hESC fate (self renewal vs. differentiation vs. death). Here, we attempt to reconcile these inconsistencies with recent reports demonstrating that an autologously produced in vitro niche regulates hESCs. Moreover, we focus on the reciprocal paracrine signals within the in vitro hESC niche allowing for the maintenance and/or expansion of the hESC colony-initiating cell (CIC). Based on this, it is clear that separation of hESC-CICs, apart from their differentiated derivatives, will be essential in future studies involving their molecular regulation. Understanding how extrinsic factors control hESC self-renewal and differentiation will allow us to culture and differentiate these pluripotent cells with higher efficiency. This knowledge will be essential for clinical applications using human pluripotent cells in regenerative medicine.


Human embryonic stem cells Niche Differentiation Self-renewal Pluripotency Signaling 



S.C.B. and M.H.S are supported by CIHR Canada Graduate Scholarship Doctoral awards, M. Bhatia by the Canadian Chair Program who holds the Canada Research Chair in human stem cell biology and Michael G. DeGroote Chair in Stem Cell Biology. Thanks to Rahul Sarugaser for insightful comments and edits.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Morag H. Stewart
    • 1
  • Sean C. Bendall
    • 1
    • 2
  • Mickie Bhatia
    • 1
    Email author
  1. 1.McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, and Department of BiochemistryMcMaster UniversityHamiltonCanada
  2. 2.Don Rix Protein Identification Facility, Department of Biochemistry, Schulich School of Medicine and DentistryUniversity of Western OntarioLondonCanada

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