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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

Models of IGN during development.(A) IGN members are highly expressed during embryogenesis but are downregulated in whole tissue as growth proceeds, while their expression is maintained in adult stem cell compartments. (B) Representation effects of the IGN on growth. Maternally expressed genes are depicted in pink and paternally expressed genes in blue. Overall effect on growth as determined by transgenic or knockout animal models is shown in green (promotion) or red (inhibition).
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pone-0026410-g004: Models of IGN during development.(A) IGN members are highly expressed during embryogenesis but are downregulated in whole tissue as growth proceeds, while their expression is maintained in adult stem cell compartments. (B) Representation effects of the IGN on growth. Maternally expressed genes are depicted in pink and paternally expressed genes in blue. Overall effect on growth as determined by transgenic or knockout animal models is shown in green (promotion) or red (inhibition).

Mentions: Many tissues undergo lifelong replenishment by rare specialized adult stem cells, which are generally quiescent, occupy unique niches, and respond rapidly to injury in order to maintain the size of a particular organ or tissue. We previously observed that a group of developmentally important imprinted genes are preferentially expressed in mouse long-term hematopoietic stem cells (LT-HSCs) compared with their differentiated counterparts [11]. Here we show that subsets of these “fingerprint” genes are core members of a network of coregulated imprinted genes, which have been implicated in the control of embryonic and early postnatal growth [16], [17]. These genes are expressed in mouse stem and progenitor cells of the hematopoietic system, skin, and skeletal muscle, and their expression is significantly lower in the differentiated progeny of these cells and in perturbed LT-HSCs. Human hematopoietic stem cells also preferentially express these genes. The imprinted genes identified in this study are highly expressed during embryonic and early postnatal life, silenced as the organism nears its adult body size [17], but remain expressed in at least three types of somatic stem cells (Figure 4A). We speculate that these imprinted genes represent a special subset of the LT-HSC “fingerprint” genes and that perhaps other somatic stem cells likewise express a larger set of “stemness” genes comprised of lineage-specific developmental regulatory genes in addition to the smaller subset of IGN members shared with other somatic stem cells.


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)

Models of IGN during development.(A) IGN members are highly expressed during embryogenesis but are downregulated in whole tissue as growth proceeds, while their expression is maintained in adult stem cell compartments. (B) Representation effects of the IGN on growth. Maternally expressed genes are depicted in pink and paternally expressed genes in blue. Overall effect on growth as determined by transgenic or knockout animal models is shown in green (promotion) or red (inhibition).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0026410-g004: Models of IGN during development.(A) IGN members are highly expressed during embryogenesis but are downregulated in whole tissue as growth proceeds, while their expression is maintained in adult stem cell compartments. (B) Representation effects of the IGN on growth. Maternally expressed genes are depicted in pink and paternally expressed genes in blue. Overall effect on growth as determined by transgenic or knockout animal models is shown in green (promotion) or red (inhibition).
Mentions: Many tissues undergo lifelong replenishment by rare specialized adult stem cells, which are generally quiescent, occupy unique niches, and respond rapidly to injury in order to maintain the size of a particular organ or tissue. We previously observed that a group of developmentally important imprinted genes are preferentially expressed in mouse long-term hematopoietic stem cells (LT-HSCs) compared with their differentiated counterparts [11]. Here we show that subsets of these “fingerprint” genes are core members of a network of coregulated imprinted genes, which have been implicated in the control of embryonic and early postnatal growth [16], [17]. These genes are expressed in mouse stem and progenitor cells of the hematopoietic system, skin, and skeletal muscle, and their expression is significantly lower in the differentiated progeny of these cells and in perturbed LT-HSCs. Human hematopoietic stem cells also preferentially express these genes. The imprinted genes identified in this study are highly expressed during embryonic and early postnatal life, silenced as the organism nears its adult body size [17], but remain expressed in at least three types of somatic stem cells (Figure 4A). We speculate that these imprinted genes represent a special subset of the LT-HSC “fingerprint” genes and that perhaps other somatic stem cells likewise express a larger set of “stemness” genes comprised of lineage-specific developmental regulatory genes in addition to the smaller subset of IGN members shared with other somatic stem cells.

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