Evidence for diversity in transcriptional profiles of single hematopoietic stem cells.

Carlos A. Ramos, Teresa V. Bowman, Nathan C. Boles, Akil A. Merchant, Yayun Zheng, Irma Parra, Suzanne A.W. Fuqua, Chad A. Shaw, Margaret A. Goodell

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Hematopoietic stem cells replenish all the cells of the blood throughout the lifetime of an animal. Although thousands of stem cells reside in the bone marrow, only a few contribute to blood production at any given time. Nothing is known about the differences between individual stem cells that dictate their particular state of activation readiness. To examine such differences between individual stem cells, we determined the global gene expression profile of 12 single stem cells using microarrays. We showed that at least half of the genetic expression variability between 12 single cells profiled was due to biological variation in 44% of the genes analyzed. We also identified specific genes with high biological variance that are candidates for influencing the state of readiness of individual hematopoietic stem cells, and confirmed the variability of a subset of these genes using single-cell real-time PCR. Because apparent variation of some genes is likely due to technical factors, we estimated the degree of biological versus technical variation for each gene using identical RNA samples containing an RNA amount equivalent to that of single cells. This enabled us to identify a large cohort of genes with low technical variability whose expression can be reliably measured on the arrays at the single-cell level. These data have established that gene expression of individual stem cells varies widely, despite extremely high phenotypic homogeneity. Some of this variation is in key regulators of stem cell activity, which could account for the differential responses of particular stem cells to exogenous stimuli. The capacity to accurately interrogate individual cells for global gene expression will facilitate a systems approach to biological processes at a single-cell level.

Original languageEnglish (US)
JournalPLoS Genetics
Volume2
Issue number9
DOIs
StatePublished - Sep 29 2006
Externally publishedYes

Fingerprint

Hematopoietic Stem Cells
stem cells
Stem Cells
stem
gene
Genes
gene expression
genes
cells
Individuality
RNA
blood
Biological Phenomena
Gene Expression
blood cells
Systems Analysis
hematopoietic stem cells
Transcriptome
bone marrow
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Evidence for diversity in transcriptional profiles of single hematopoietic stem cells. / Ramos, Carlos A.; Bowman, Teresa V.; Boles, Nathan C.; Merchant, Akil A.; Zheng, Yayun; Parra, Irma; Fuqua, Suzanne A.W.; Shaw, Chad A.; Goodell, Margaret A.

In: PLoS Genetics, Vol. 2, No. 9, 29.09.2006.

Research output: Contribution to journalArticle

Ramos, CA, Bowman, TV, Boles, NC, Merchant, AA, Zheng, Y, Parra, I, Fuqua, SAW, Shaw, CA & Goodell, MA 2006, 'Evidence for diversity in transcriptional profiles of single hematopoietic stem cells.', PLoS Genetics, vol. 2, no. 9. https://doi.org/10.1371/journal.pgen.0020159
Ramos, Carlos A. ; Bowman, Teresa V. ; Boles, Nathan C. ; Merchant, Akil A. ; Zheng, Yayun ; Parra, Irma ; Fuqua, Suzanne A.W. ; Shaw, Chad A. ; Goodell, Margaret A. / Evidence for diversity in transcriptional profiles of single hematopoietic stem cells. In: PLoS Genetics. 2006 ; Vol. 2, No. 9.
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