TY - JOUR
T1 - Hematopoietic Fingerprints
T2 - An Expression Database of Stem Cells and Their Progeny
AU - Chambers, Stuart M.
AU - Boles, Nathan C.
AU - Lin, Kuan Yin K.
AU - Tierney, Megan P.
AU - Bowman, Teresa V.
AU - Bradfute, Steven B.
AU - Chen, Alice J.
AU - Merchant, Akil A.
AU - Sirin, Olga
AU - Weksberg, David C.
AU - Merchant, Mehveen G.
AU - Fisk, C. Joseph
AU - Shaw, Chad A.
AU - Goodell, Margaret A.
N1 - Funding Information:
We thank all Goodell lab members for helpful comments. The work was supported by DK63588 and DK58192, and M.A.G. was a Scholar of the Leukemia and Lymphoma Society. S.M.C. was supported by T32 AG000183. K.-Y.K.L., D.C.W., and M.P.T. were partially supported by T32 DK064717. S.B.B. was supported by T32 AI07495. We thank Dr. Zhou Songyang at BCM for providing the MSCV-IRES-GFP backbone and the pCL-Eco packaging vectors.
PY - 2007/11/15
Y1 - 2007/11/15
N2 - Hematopoietic stem cells (HSCs) continuously regenerate the hematologic system, yet few genes regulating this process have been defined. To identify candidate factors involved in differentiation and self-renewal, we have generated an expression database of hematopoietic stem cells and their differentiated progeny, including erythrocytes, granulocytes, monocytes, NK cells, activated and naive T cells, and B cells. Bioinformatic analysis revealed HSCs were more transcriptionally active than their progeny and shared a common activation mechanism with T cells. Each cell type also displayed unique biases in the regulation of particular genetic pathways, with Wnt signaling particularly enhanced in HSCs. We identified ∼100-400 genes uniquely expressed in each cell type, termed lineage "fingerprints." In overexpression studies, two of these genes, Zfp105 from the NK cell lineage, and Ets2 from the monocyte lineage, were able to significantly influence differentiation toward their respective lineages, demonstrating the utility of the fingerprints for identifying genes that regulate differentiation.
AB - Hematopoietic stem cells (HSCs) continuously regenerate the hematologic system, yet few genes regulating this process have been defined. To identify candidate factors involved in differentiation and self-renewal, we have generated an expression database of hematopoietic stem cells and their differentiated progeny, including erythrocytes, granulocytes, monocytes, NK cells, activated and naive T cells, and B cells. Bioinformatic analysis revealed HSCs were more transcriptionally active than their progeny and shared a common activation mechanism with T cells. Each cell type also displayed unique biases in the regulation of particular genetic pathways, with Wnt signaling particularly enhanced in HSCs. We identified ∼100-400 genes uniquely expressed in each cell type, termed lineage "fingerprints." In overexpression studies, two of these genes, Zfp105 from the NK cell lineage, and Ets2 from the monocyte lineage, were able to significantly influence differentiation toward their respective lineages, demonstrating the utility of the fingerprints for identifying genes that regulate differentiation.
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=35848943273&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35848943273&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2007.10.003
DO - 10.1016/j.stem.2007.10.003
M3 - Article
C2 - 18371395
AN - SCOPUS:35848943273
SN - 1934-5909
VL - 1
SP - 578
EP - 591
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 5
ER -