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Prospects Defining the hematopoietic stem cell niche: The chicken and the egg conundrum 1 1 1 1* Sofie Singbrant , Maria Askmyr , Louise E. Purton Carl R. Walkley 1St. Vincent’s Institute of Medical Research Department of Medicine at St. Vincent’s Hospital, University of Melbourne, Victoria, Australia. *Correspondence should be addressed to: Carl Walkley St Vincent’s Institute, 9 Princes Street, Fitzroy, Victoria 3065 Australia E-mail: cwalkley@svi.edu.au Phone: +61 3 9288 2480, Fax: +61 3 9416 2676 Received 16 February 2011; Accepted 18 February 2011 Journal of Cellular Biochemistry © 2011 Wiley-Liss, Inc. DOI 10.1002/jcb.23085 1 Abstract Understanding the in vivo regulation of hematopoietic stem cells (HSC) will be critical to identifying key factors involved in the regulation of HSC self-renewal and differentiation. The niche (microenvironment) in which HSCs reside has recently regained attention accompanied by a dramatic increase in the understanding of the cellular constituents of the bone marrow HSC niche. The use of sophisticated genetic models allowing modulation of specific lineages has demonstrated roles for mesenchymal derived elements such as osteoblasts and adipocytes, vasculature, nerves and a range of hematopoietic progeny of the HSC as being participants in the regulation of the bone marrow microenviro