Permissiveness to form pluripotent stem cells may be an evolutionarily derived characteristic in Mus musculus

Garbutt, Tiffany A.; Konneker, Thomas; Konganti, Kranti; Hillhouse, Andrew; Swift-Haire, Francis; Jones, Alexis; Phelps, Drake; Aylor, David L.; Threadgill, David W.

doi:10.1038/s41598-018-32116-8

Cited by 12 publications

(12 citation statements)

References 53 publications

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“…Companion resources including tissue and cell line biobanks are being generated for these populations. One emerging resource, a set of stem cell lines including mouse embryonic stem cells (mESCs) and induced pluripotent stem cells (iPSCs) derived from these populations [89,90], enables in vitro systems genetics and molecular phenotyping QTL validation.…”

Section: Resources For Discovery and Validationmentioning

confidence: 99%

High-Diversity Mouse Populations for Complex Traits

et al. 2019

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Contemporary mouse genetic reference populations are a powerful platform to discover complex disease mechanisms. Advanced high-diversity mouse populations include the Collaborative Cross (CC) strains, Diversity Outbred (DO) stock, and their isogenic founder strains. When used in systems genetics and integrative genomics analyses, these populations efficiently harnesses known genetic variation for precise and contextualized identification of complex disease mechanisms. Extensive genetic, genomic, and phenotypic data are already available for these high-diversity mouse populations and a growing suite of data analysis tools have been developed to support research on diverse mice. This integrated resource can be used to discover and evaluate disease mechanisms relevant across species. The Challenge of Complex Disease Complex diseases present compelling biomedical challenges that can be studied using human and nonhuman animal genetics. Although advances in human genetics have identified loci for many heritable complex diseases [1-8], there are several well-known limitations of genomewide association studies (GWASs). (i) For many human disease loci, the biological mechanism of action is unknown. (ii) When little is known about a locus, the path from genetic association to clinically actionable targets is unclear. (iii) Disease process or developmental trajectory is not always obvious from a causal genetic variant. (iv) GWAS results may not generalize across human subpopulations. (v) Medical records and participant phenotyping is often incomplete, imprecise, and retrospective, whereas model organism phenotyping can include in-depth, prospective, and standardized measures. (vi) Sample size requirements are formidable in human GWASs. (vii) Power is insufficient to study interacting genetic loci. (viii) Studies of genetic interaction with development, environment, and sex are largely intractable. Further, heterogeneous diseases like psychiatric disorders manifest with overlapping symptoms, intertwined disease trajectories [9], and complex genetic regulation [9,10]. In summary, the SNP-to-disease association model underlying GWASs cannot readily capture complex disease biology without further biological context. These challenges are often tractable with discovery genetics in model organisms.

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Section: Resources For Discovery and Validationmentioning

confidence: 99%

High-Diversity Mouse Populations for Complex Traits

et al. 2019

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“…Similarly, different supplementation regimes are required for ESC and iPSC establishment in nonpermissive strains of mice. It has been suggested that the permissiveness to ESC derivation under relatively simple LIF conditions is an evolutionarily derived characteristic in M. musculus that is not shared with other eutherian mammals (Garbutt et al, ). This lack of effectiveness of protocols established in the standard murine and human ESC models is one of the main challenges for researchers working with domestic and exotic species.…”

Section: Discussionmentioning

confidence: 99%

“…Human ESC can be transformed to a state similar to mouse ESC by activating the LIF/ STAT3 pathway, but human ESC will differentiate if support from the MEK/ERK pathway is removed (Nichols & Smith, 2009;Rossello, Pfenning, Howard, & Hochgeschwender, 2016). In cats, neither supplementation of LIF nor fibroblast growth factor 2 (FGF2) supported the long-term maintenance of pluripotency in cells derived from ICM (Gómez et al, 2010;Yu et al, 2008;Zhou et al, 2019) that is not shared with other eutherian mammals (Garbutt et al, 2018). This lack of effectiveness of protocols established in the standard murine and human ESC models is one of the main challenges for researchers working with domestic and exotic species.…”

Section: Discussionmentioning

confidence: 99%

Endogenous pluripotent factor expression after reprogramming cat fetal fibroblasts using inducible transcription factors

Zhou

Comizzoli

Keefer

2019

Molecular Reproduction Devel

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Incomplete transgene‐silencing remains a challenge in the generation of induced pluripotent stem cells (iPSC) in felids—a critical family in biomedical and biodiversity conservation science. In this study doxycycline‐inducible transgenes (NANOG, POU5F1, SOX2, KLF4, and cMYC) were used to reprogram cat fetal fibroblasts with the objective of obtaining iPSC with fully silenced transgenes. Colony formation was slower (14 vs. 8 days) and at lower efficiency than mouse embryonic fibroblasts (0.002% vs. 0.02% of seeded cells). Alkaline‐phosphatase positive colonies were grown on feeder cells plus LIF and GSK3, MEK, and ROCK inhibitors. Cells could be passaged singly and transgene expression was silenced at passage 3 (P3) after doxycycline removal at P2. NANOG, POU5F1, and SOX2 were expressed at P3, P6, and P10, although at lower immunostaining intensities than in cat inner cell masses (ICM). Transcripts related to pluripotency (NANOG, POU5F1, SOX2, KLF4, cMYC, and REX1) and differentiation (FGF5, TBXT, GATA6, SOX17, FOXF1, PAX6, and SOX1) were assessed by a reverse transcription‐quantitative polymerase chain reaction in iPSC and embryoid bodies. The immunostaining patterns, relatively low levels of NANOG and REX1 in comparison to ICM along with the expression of TBXT (mesoderm) suggested that cells were a mix of reprogrammed pluripotent and differentiating cells.

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“…There are a variety of available model organism GRPs, and ultimately the choice of GRP depends not only on the ability of that organism to appropriately and economically model a particular disease but also on the diversity, strength, and haplotype structure of the alleles segregating in the population. Cellular GRPs can be created by deriving cell lines ('in vitro') or culturing primary cells ('ex vivo') directly from a genetically diverse population, thereby capturing the resident natural variation in those individuals [10][11][12][13]. The development and application of these cellular panels are active areas of genetic resource and technology development.…”

Section: Cellular Models From Grpsmentioning

confidence: 99%