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Imprinted genes that regulate early mammalian growth are coexpressed in somatic stem cells.

Berg JS, Lin KK, Sonnet C, Boles NC, Weksberg DC, Nguyen H, Holt LJ, Rickwood D, Daly RJ, Goodell MA - PLoS ONE (2011)

Bottom Line: Here, we scrutinized data comparing genes expressed in murine long-term hematopoietic stem cells with their differentiated counterparts and observed that a disproportionate number were members of the developmentally-important, monoallelically expressed imprinted genes.Studying a subset, which are members of a purported imprinted gene network (IGN), we found their expression in HSCs rapidly altered upon hematopoietic perturbations.The parallel down-regulation of these genes postnatally in response to proliferation and differentiation suggests that the IGN could play a mechanistic role in both cell growth and tissue homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.

ABSTRACT
Lifelong, many somatic tissues are replenished by specialized adult stem cells. These stem cells are generally rare, infrequently dividing, occupy a unique niche, and can rapidly respond to injury to maintain a steady tissue size. Despite these commonalities, few shared regulatory mechanisms have been identified. Here, we scrutinized data comparing genes expressed in murine long-term hematopoietic stem cells with their differentiated counterparts and observed that a disproportionate number were members of the developmentally-important, monoallelically expressed imprinted genes. Studying a subset, which are members of a purported imprinted gene network (IGN), we found their expression in HSCs rapidly altered upon hematopoietic perturbations. These imprinted genes were also predominantly expressed in stem/progenitor cells of the adult epidermis and skeletal muscle in mice, relative to their differentiated counterparts. The parallel down-regulation of these genes postnatally in response to proliferation and differentiation suggests that the IGN could play a mechanistic role in both cell growth and tissue homeostasis.

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Related in: MedlinePlus

Summary of microarray analysis of imprinted gene expression in hematopoiesis.Microarray data from mouse LT-HSCs and differentiated lineages [11] were analyzed for the expression of known imprinted genes. The chart (left) shows the distribution of genes according to the specificity of their lineage distribution; the individual genes in each expression category are listed to the right (genes previously identified as being part of the IGN, as defined by Varrault et al. [16] are noted in bold-face type). Supplementary information is provided in Table S1, showing the description of the core IGN genes in this study.
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pone-0026410-g001: Summary of microarray analysis of imprinted gene expression in hematopoiesis.Microarray data from mouse LT-HSCs and differentiated lineages [11] were analyzed for the expression of known imprinted genes. The chart (left) shows the distribution of genes according to the specificity of their lineage distribution; the individual genes in each expression category are listed to the right (genes previously identified as being part of the IGN, as defined by Varrault et al. [16] are noted in bold-face type). Supplementary information is provided in Table S1, showing the description of the core IGN genes in this study.

Mentions: Recognition that several imprinted genes were represented in the gene expression profile we had generated for mouse long-term repopulating hematopoietic stem cells (LT-HSCs) [11] led us to ask whether such genes might play a critical role in the regulation of LT-HSCs and perhaps of other adult stem cells as well. Close examination of the data for each of the hematopoietic cell types previously analyzed in our lab by microarray revealed that imprinted genes, although constituting only 65 (∼0.33%) of the ∼20,000 genes represented on our expression microarrays, accounted for 8 (3.2%) of the 253 genes in a stringently annotated list of “fingerprint” genes expressed exclusively in LT-HSCs, a nearly 10-fold enrichment relative to that expected by chance (P<0.0001 by Fisher's exact test). Five other imprinted genes were expressed predominantly in LT-HSCs with much lower expression in a small subset of differentiated lineages. Thus, an unusually high proportion of known imprinted genes are preferentially expressed in LT-HSCs (Figure 1).


Imprinted genes that regulate early mammalian growth are coexpressed in somatic stem cells.

Berg JS, Lin KK, Sonnet C, Boles NC, Weksberg DC, Nguyen H, Holt LJ, Rickwood D, Daly RJ, Goodell MA - PLoS ONE (2011)

Summary of microarray analysis of imprinted gene expression in hematopoiesis.Microarray data from mouse LT-HSCs and differentiated lineages [11] were analyzed for the expression of known imprinted genes. The chart (left) shows the distribution of genes according to the specificity of their lineage distribution; the individual genes in each expression category are listed to the right (genes previously identified as being part of the IGN, as defined by Varrault et al. [16] are noted in bold-face type). Supplementary information is provided in Table S1, showing the description of the core IGN genes in this study.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198398&req=5

pone-0026410-g001: Summary of microarray analysis of imprinted gene expression in hematopoiesis.Microarray data from mouse LT-HSCs and differentiated lineages [11] were analyzed for the expression of known imprinted genes. The chart (left) shows the distribution of genes according to the specificity of their lineage distribution; the individual genes in each expression category are listed to the right (genes previously identified as being part of the IGN, as defined by Varrault et al. [16] are noted in bold-face type). Supplementary information is provided in Table S1, showing the description of the core IGN genes in this study.
Mentions: Recognition that several imprinted genes were represented in the gene expression profile we had generated for mouse long-term repopulating hematopoietic stem cells (LT-HSCs) [11] led us to ask whether such genes might play a critical role in the regulation of LT-HSCs and perhaps of other adult stem cells as well. Close examination of the data for each of the hematopoietic cell types previously analyzed in our lab by microarray revealed that imprinted genes, although constituting only 65 (∼0.33%) of the ∼20,000 genes represented on our expression microarrays, accounted for 8 (3.2%) of the 253 genes in a stringently annotated list of “fingerprint” genes expressed exclusively in LT-HSCs, a nearly 10-fold enrichment relative to that expected by chance (P<0.0001 by Fisher's exact test). Five other imprinted genes were expressed predominantly in LT-HSCs with much lower expression in a small subset of differentiated lineages. Thus, an unusually high proportion of known imprinted genes are preferentially expressed in LT-HSCs (Figure 1).

Bottom Line: Here, we scrutinized data comparing genes expressed in murine long-term hematopoietic stem cells with their differentiated counterparts and observed that a disproportionate number were members of the developmentally-important, monoallelically expressed imprinted genes.Studying a subset, which are members of a purported imprinted gene network (IGN), we found their expression in HSCs rapidly altered upon hematopoietic perturbations.The parallel down-regulation of these genes postnatally in response to proliferation and differentiation suggests that the IGN could play a mechanistic role in both cell growth and tissue homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.

ABSTRACT
Lifelong, many somatic tissues are replenished by specialized adult stem cells. These stem cells are generally rare, infrequently dividing, occupy a unique niche, and can rapidly respond to injury to maintain a steady tissue size. Despite these commonalities, few shared regulatory mechanisms have been identified. Here, we scrutinized data comparing genes expressed in murine long-term hematopoietic stem cells with their differentiated counterparts and observed that a disproportionate number were members of the developmentally-important, monoallelically expressed imprinted genes. Studying a subset, which are members of a purported imprinted gene network (IGN), we found their expression in HSCs rapidly altered upon hematopoietic perturbations. These imprinted genes were also predominantly expressed in stem/progenitor cells of the adult epidermis and skeletal muscle in mice, relative to their differentiated counterparts. The parallel down-regulation of these genes postnatally in response to proliferation and differentiation suggests that the IGN could play a mechanistic role in both cell growth and tissue homeostasis.

Show MeSH
Related in: MedlinePlus