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Insights from a chimpanzee adipose stromal cell population: opportunities for adult stem cells to expand primate functional genomics.

Pfefferle LW, Wray GA - Genome Biol Evol (2013)

Bottom Line: Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution.In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates.By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University.

ABSTRACT
Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs with three comparable human cell lines. Consistent with previous studies on ASCs in humans, the chimpanzee cells have fibroblast-like morphology and express genes encoding components of the extracellular matrix at high levels. Differentially expressed genes are enriched for distinct functional classes between species: immunity and protein processing are higher in chimpanzees, whereas cell cycle and DNA processing are higher in humans. Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution. In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates. By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling.

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Transcriptomic insights into chimpanzee ASCs. (A) Highest expressed genes using FPKM. (B) KEGG pathway: ECM–receptor interaction. Highlighted genes have FPKM ≥100 and the connections that contain a complete ECM-ligand and receptor pair are shown in bold. Immunoglobin superfamily is not shown.
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evt148-F3: Transcriptomic insights into chimpanzee ASCs. (A) Highest expressed genes using FPKM. (B) KEGG pathway: ECM–receptor interaction. Highlighted genes have FPKM ≥100 and the connections that contain a complete ECM-ligand and receptor pair are shown in bold. Immunoglobin superfamily is not shown.

Mentions: To uncover fundamental properties of the chimpanzee ASC transcriptome, RNA extracted from the confluent chimpanzee stromal cells (figs. 1B and 2A) was made into Illumina TruSeq libraries for RNA-Seq. Approximately 48 million reads were mapped (∼94% of the total) to the panTro3 chimpanzee genome assembly. The highest expressed genes in chimpanzee ASC overwhelmingly encode extracellular matrix (ECM) components (fig. 3A). This makes sense, as cells of the connective tissue produce, organize, and degrade the ECM. In turn, the ECM provides organization, strength, and signaling mechanisms for cells of the connective tissue. The dominance of ECM gene expression we observe in chimpanzee ASCs is consistent with a previous study of human ASCs (Katz et al. 2005). We also observed that the 10 highest expressed genes in chimpanzee were represented within the top 14 highest expressed genes in humans (fig. 3A). It is not surprising that genes encoding collagen, the most abundant family of proteins in mammals and primary source of strength and structure in the ECM, represent five of the top ten highest expressed genes (fig. 3A) (Alberts et al. 2008).Fig. 3.—


Insights from a chimpanzee adipose stromal cell population: opportunities for adult stem cells to expand primate functional genomics.

Pfefferle LW, Wray GA - Genome Biol Evol (2013)

Transcriptomic insights into chimpanzee ASCs. (A) Highest expressed genes using FPKM. (B) KEGG pathway: ECM–receptor interaction. Highlighted genes have FPKM ≥100 and the connections that contain a complete ECM-ligand and receptor pair are shown in bold. Immunoglobin superfamily is not shown.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814206&req=5

evt148-F3: Transcriptomic insights into chimpanzee ASCs. (A) Highest expressed genes using FPKM. (B) KEGG pathway: ECM–receptor interaction. Highlighted genes have FPKM ≥100 and the connections that contain a complete ECM-ligand and receptor pair are shown in bold. Immunoglobin superfamily is not shown.
Mentions: To uncover fundamental properties of the chimpanzee ASC transcriptome, RNA extracted from the confluent chimpanzee stromal cells (figs. 1B and 2A) was made into Illumina TruSeq libraries for RNA-Seq. Approximately 48 million reads were mapped (∼94% of the total) to the panTro3 chimpanzee genome assembly. The highest expressed genes in chimpanzee ASC overwhelmingly encode extracellular matrix (ECM) components (fig. 3A). This makes sense, as cells of the connective tissue produce, organize, and degrade the ECM. In turn, the ECM provides organization, strength, and signaling mechanisms for cells of the connective tissue. The dominance of ECM gene expression we observe in chimpanzee ASCs is consistent with a previous study of human ASCs (Katz et al. 2005). We also observed that the 10 highest expressed genes in chimpanzee were represented within the top 14 highest expressed genes in humans (fig. 3A). It is not surprising that genes encoding collagen, the most abundant family of proteins in mammals and primary source of strength and structure in the ECM, represent five of the top ten highest expressed genes (fig. 3A) (Alberts et al. 2008).Fig. 3.—

Bottom Line: Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution.In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates.By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University.

ABSTRACT
Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs with three comparable human cell lines. Consistent with previous studies on ASCs in humans, the chimpanzee cells have fibroblast-like morphology and express genes encoding components of the extracellular matrix at high levels. Differentially expressed genes are enriched for distinct functional classes between species: immunity and protein processing are higher in chimpanzees, whereas cell cycle and DNA processing are higher in humans. Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution. In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates. By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling.

Show MeSH