GRP94 Regulates Stem Cell-Niche Interactions Figure 9. Effect of cKO microenvironment on HSC maintenance. A) Scheme of creating chimeric mice with WT hematopoietic cells transplanted into WT or cKO microenvironment. B) Complete blood count with tail peripheral blood from WT-WT (n = 5) and WT-cKO (n = 8) chimeric mice. C) Quantitation of spleen weights from WT-WT (n = 4) and WT-cKO (n = 5) chimeric mice. D) Representative flow cytometric analysis with BM from WT-WT and WT-cKO chimeric mice using Lin, c-Kit and Sca-1. E) Summary of percentage of LSK cells in the BM from WT-WT (n = 5) and WT-cKO (n = 8) chimeric mice. All data are presented as mean 6 s.e.. doi:10.1371/journal.pone.0020364.g009 and cell surface proteins are synthesized in the rough ER where they are folded into their functional conformation by ER chaperone proteins. Therefore, ER chaperone proteins are likely to be important for maintaining hematopoiesis, and their function depends on the role of specific client proteins in hematopoiesis. Other than synthesizing client proteins that are regulating hematopoiesis, the ER is also involved in hematopoiesis through UPR signaling pathways. For example, UPR sensor IRE1 ribonuclease activity for XBP-1 splicing is required for both the early differentiation of T and B lymphocytes and the terminal differentiation of activated B cells to immunoglobin-secreted plasma cells [53,54]. Whether UPR signaling is involved in PLoS ONE | www.plosone.org 10 May 2011 | Volume 6 | Issue 5 | e20364