Transcriptome of Human Hematopoietic Stem Cells

The human CD34+/CD38-/Lin- cell subset comprises ~1-10% of the CD34+ cell population and includes few of the less primitive hematopoietic (lineage-committed) progenitor cells (HPCs), yet contains most of the primitive in vivo engrafting (lympho-) hematopoietic stem cells (HSCs). We analyzed gene expression in CD34+/CD38-/Lin- cell populations isolated from bone marrow (BM), placental/umbilical cord blood (CB), and mobilized peripheral blood stem-progenitor cell (PBSC) preparations from normal human donors. 4746 genes were expressed in CD34+/CD38-/Lin- cells from all three tissues. We also isolated and determined the genes expressed in the stem cell-depleted, progenitor cell-enriched CD34+/[CD38/Lin]++ cell population from each tissue. Comparison of the transcripts expressed in CD34+/CD38-/Lin- (HSC-enriched) versus CD34+/[CD38/Lin]++ (HSC-depleted) cells from each tissue yielded 81 genes that were over-represented and 90 genes under-represented in the transcriptome (i.e., global gene expression profile) of all three of the CD34+/CD38-/Lin- cell populations. These transcripts include a number of known genes (e.g., transcription factors, receptors, and signaling molecules) and unknown genes that may play roles in survival, self-renewal, differentiation and/or migration/adhesion of human HSCs. Notably, CD52 was highly over-represented in the CD34+/CD38-/Lin- population. Preliminary immunostaining and flow cytometry experiments revealed CD52++ and CD52- subpopulations within the CD34+/CD38-/Lin- population, suggesting that CD52 may be a marker for further purification of hematopoietic stem-progenitor (HSPC) subpopulations. Description (Set) Proposed Use (Set) Identification of genes that are functionally important in stem or progenitor cells. Identification of gene encoding proteins that may be markers for stem or progenitor cells. Identification of the near-full transcriptomic signature of stem and progenitor cells. Patent (Set) WO 2004/071464

Inventor(s): Civin, Curt I.

Type of Offer: Licensing



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