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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 01, 2007 |
| Title |
Elucidation of the phenotypic, functional and molecular topography of a myeloerythroid progenitor cell hierarchy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The major myeloid blood cell lineages, including erythrocytes, platelets, granulocytes and macrophages, are generated from hematopoietic stem cells (HSC) by differentiation through a series of increasingly more committed progenitor cells. Precise phenotypic identification and functional characterization of such intermediate progenitors has important consequences for understanding fundamental differentiation processes and is clinically relevant since such events become dysregulated in various disease settings, including leukemia. While previous studies have suggested a hierarchy for myeloid differentiation involving a common progenitor through which all myeloid lineages are derived, several recent studies have suggested that such a developmental intermediate might not be an absolute requirement. Here, we evaluated the functional in vitro and in vivo potentials of a range of prospectively isolated myeloid precursors with differential expression of CD150, Endoglin and CD41. Our studies reveal a complex hierarchy of myeloerythroid progenitors with distinct and developmentally restricted lineage potentials. Global gene expression signatures of these cellular subsets revealed expression patterns consistent with their functional capacities, while hierarchical clustering analysis provides details on their lineage relationships. These data challenge existing models of hematopoietic differentiation, by suggesting that progenitors of the innate and adaptive immune system in the adult separate late, and to a large extent, following the divergence of megakaryocytic/erythroid potential.
Keywords: global gene expression profiling of prospectively isolated murine bone marrow progenitor subset by usage of affymetrix
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| Overall design |
RNA was extracted from purified adult BM subsets using RNeasy mRNA purification kit (Qiagen). Subsequent handling was performed at the SweGene Affymetrix unit at Lund University (http://www.swegene.org/microarray). Briefly, RNA (arrays in triplicate for all progenitor fractions except for pre MegE for which 5 arrays were produced) was labeled and amplified according to AffymetrixTM; Small Sample Labelling Protocol v.2, with the exception that the second round of in vitro transcription (IVT) was performed using AffymetrixTM GeneChipTM Expression 3’amplification kit. Hybridization and washing was performed according to AffymetrixTM GeneChipTM Expression analysis technical manual. Chips were scanned using an AffymetrixTM GeneChipTM Scanner 3000 and scaled to a median intensity of 100. For subsequent analysis, probe level expression values were extracted using RMA (Irizarry et al., 2003) and subsequent analyses was performed using dChip software (http://biosun1.harvard.edu/complab/dchip/) following filtering (0.5<SD/mean<1,000).
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| Contributor(s) |
Pronk CJ, Rossi DJ, Månsson R, Attema JL, Logi Norddahl G, Kwok Fai Chan C, Sigvardsson M, Bryder D |
| Citation(s) |
18371379 |
| Submission date |
Jul 09, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Robert Månsson |
| E-mail(s) |
robert.mansson@ki.se
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| Organization name |
Lund University
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| Department |
Hemapotoietic stem cell biology
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| Street address |
Klinikgatan 26, BMC B12
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| City |
Lund |
| ZIP/Postal code |
221 84 |
| Country |
Sweden |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (17)
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| GSM207676 |
Adult murine BM, Lin-Sca1lowKitlowIL7r+Flk2+ 1 |
| GSM207677 |
Adult murine BM, Lin-Sca1lowKitlowIL7r+Flk2+ 2 |
| GSM207678 |
Adult murine BM, Lin-Sca1lowKitlowIL7r+Flk2+ 3 |
| GSM207679 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1-Englow 1 |
| GSM207680 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1-Englow 2 |
| GSM207681 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1-Englow 3 |
| GSM207682 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Englow 1 |
| GSM207683 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Englow 2 |
| GSM207684 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Englow 3 |
| GSM207685 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Englow 4 |
| GSM207686 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Englow 5 |
| GSM207687 |
Adult murine BM, Lin-Sca1-Kit+Itga2b+Slamf1+ 1 |
| GSM207688 |
Adult murine BM, Lin-Sca1-Kit+Itga2b+Slamf1+ 2 |
| GSM207689 |
Adult murine BM, Lin-Sca1-Kit+Itga2b+Slamf1+ 3 |
| GSM207690 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Enghigh 1 |
| GSM207691 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Enghigh 2 |
| GSM207692 |
Adult murine BM, Lin-Sca1-Kit+Itga2b-FcgRlowSlamf1+Enghigh 3 |
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| Relations |
| BioProject |
PRJNA101465 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8407_RAW.tar |
94.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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