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. 2005 Sep;1(3):e28.
doi: 10.1371/journal.pgen.0010028.

Differential expression of novel potential regulators in hematopoietic stem cells

E Camilla Forsberg  1 , Susan S Prohaska, Sol Katzman, Garrett C Heffner, Josh M Stuart, Irving L Weissman
Affiliations

Differential expression of novel potential regulators in hematopoietic stem cells

E Camilla Forsberg et al. PLoS Genet. 2005 Sep.

Abstract

The hematopoietic system is an invaluable model both for understanding basic developmental biology and for developing clinically relevant cell therapies. Using highly purified cells and rigorous microarray analysis we have compared the expression pattern of three of the most primitive hematopoietic subpopulations in adult mouse bone marrow: long-term hematopoietic stem cells (HSC), short-term HSC, and multipotent progenitors. All three populations are capable of differentiating into a spectrum of mature blood cells, but differ in their self-renewal and proliferative capacity. We identified numerous novel potential regulators of HSC self-renewal and proliferation that were differentially expressed between these closely related cell populations. Many of the differentially expressed transcripts fit into pathways and protein complexes not previously identified in HSC, providing evidence for new HSC regulatory units. Extending these observations to the protein level, we demonstrate expression of several of the corresponding proteins, which provide novel surface markers for HSC. We discuss the implications of our findings for HSC biology. In particular, our data suggest that cell-cell and cell-matrix interactions are major regulators of long-term HSC, and that HSC themselves play important roles in regulating their immediate microenvironment.

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Conflict of interest statement

Competing interests. As a former advisory board member of Amgen, ILW owns significant Amgen stock. He also cofounded and consulted for Systemix; cofounded Cellerant Therapeutics, a spin-off from Systemix Novartis to transplant human HSC; and is a cofounder and a director of the company Stem Cells, which is involved in the isolation and study of human central nervous system stem cells, liver-repopulating cells, and pancreatic islet/progenitor cells.

Figures

Figure 1
Figure 1. Top 25 Differentially Regulated Transcripts with Corresponding SAM Plots for Each Comparison
Only known, unique genes are listed; thus, ESTs were removed, and genes appearing more than once in the same list are denoted with number of appearances in parentheses. An “A” in parenthesis indicates that results from analogous experiments using Agilent arrays are consistent with the Stanford Microarray Database array data. The LT-HSC to ST-HSC comparison was not performed with Agilent arrays.
Figure 2
Figure 2. Heat Map Representation of Differentially Regulated Transcripts
Rows represent genes and columns represent array comparisons between cell populations as indicated. (A) Significance score by SAM is indicated from top to bottom of each comparison (n = 6) by gradients of yellow or blue, with brighter yellow or blue indicating higher significance. Yellow or blue in additional columns indicate that the gene was also differentially expressed between these cell types (e.g., many of the genes upregulated in MPP versus LT-HSC were also upregulated in ST-HSC compared to LT-HSC). (B) Conventional red-green expression data for all the differentially regulated genes for each array. Red indicates genes upregulated in the more differentiated cell population (e.g., upregulated in MPP when compared to LT-HSC); green indicates upregulated in the less differentiated cell population.
Figure 3
Figure 3. Flow Cytometric Analysis of Cell Surface Protein Levels on LT-HSC, ST-HSC, and MPP Relative to Control
Green represents LT-HSC, blue represents ST-HSC, red represents MPP, and grey represents the control.
Figure 4
Figure 4. Hypothetical Model of Selected Potential Interactions of Proteins Corresponding to Differentially Expressed Transcripts
Molecules upregulated in LT-HSC are in green; those upregulated in MPP are red. Depicted protein interactions and colocalization are based on published reports in various mammalian and nonmammalian systems. Single cells expressing all the proteins as depicted in this cartoon may not exist. Not drawn to scale.
Figure 5
Figure 5. Schematic of Biological Processes that Gradually Decline or Increase with LT-HSC Differentiation Based on the Relative Transcript Levels Presented in this Report
Green circles represent LT-HSC, and color gradients from green to red represent increasingly mature progeny.
See this image and copyright information in PMC

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References

    1. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, et al. A stem cell molecular signature. Science. 2002;298:601–604. - PubMed
    1. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA. “Stemness”: Transcriptional profiling of embryonic and adult stem cells. Science. 2002;298:597–600. - PubMed
    1. Venezia TA, Merchant AA, Ramos CA, Whitehouse NL, Young AS, et al. Molecular signatures of proliferation and quiescence in hematopoietic stem cells. PLoS Biol. 2004;2:e301. - PMC - PubMed
    1. Terskikh AV, Miyamoto T, Chang C, Diatchenko L, Weissman IL. Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood. 2003;102:94–101. - PubMed
    1. Akashi K, He X, Chen J, Iwasaki H, Niu C, et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood. 2003;101:383–389. - PubMed

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