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| Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics' |
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| Author(s): Bystrykh L, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang JT, Manly KF, Lu L, Chesler EJ, Alberts R, Jansen RC, Williams RW, Cooke MP, de Haan G |
| Source: NATURE GENETICS Volume: 37 Issue: 3 Pages: 225-232 Published: MAR 2005 |
| Times Cited: 197 References: 27 |
| Abstract: We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue- specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts. |
| Document Type: Article |
| Language: English |
| Reprint Address: de Haan, G (reprint author), Univ Groningen, Dept Stem Cell Biol, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands |
Addresses:
1. Univ Groningen, Dept Stem Cell Biol, NL-9713 AV Groningen, Netherlands
2. Novartis Res Fdn, Gen Inst, San Diego, CA 92121 USA
3. Acad Hosp, Dept Haematol, Groningen, Netherlands
4. Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA
5. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA
6. Univ Groningen, Groningen Bioinformat Ctr, Groningen, Netherlands |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 901QU |
| ISSN: 1061-4036 |
| DOI: 10.1038/ng1497 |
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