Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells

By J. Polo, Susanna Liu, Maria E. Figueroa, Warakorn Kulalert, S. Eminli, K. Tan, E. Apostolou, M. Stadtfeld, Yushan Li, T. Shioda and 5 more. Nature Biotechnology, 2010

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Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ca065de8535dae01e99283c049ac678061f006c4

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Citations in the corpus

Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines (2011, neutral): “To match the passage numbers of the 20 ES cell lines and to avoid increased noise in extremely low-passage iPS cell lines (Chin et al., 2009; Polo et al., 2010), we focused our analysis on iPS cells in the range of passage 15 to passage 30 (Table S1).”
Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications (2019, background): “Although it has been documented that each ESC line has its own clonal differences, iPSC lines show greater diversity than ESCs due to the residual epigenetic memory, genetic background and the characteristics acquired during reprogramming and differentiation [62,63,96].”
Emerging trends and new developments in regenerative medicine: a scientometric update (2000 – 2014) (2014, neutral): “1 Warren et al. (2010) CELL STEM CELL, V7, P618 [45] 113.0 2011 2014 2 Kim et al. (2010) NATURE, V467, P285 [32] 102.8 2011 2014 3 Vierbuchen et al. (2010) NATURE, V463, P1035 [23] 93.7 2011 2014 4 Ieda et al. (2010) CELL, V142, P375 [22] 90.7 2011 2014 5 Lister et al. (2011) NATURE, V471, P68 [46] ”
Induced pluripotency: history, mechanisms, and applications. (2010, background): “…mouse iPSCs harbor epigenetic abnormalities (Stadtfeld et al. 2010b) and retain a transient epigenetic memory of their donor cells (Kim et al. 2010; Polo et al. 2010) will require a careful molecular and functional evaluation of human iPSCs for similar potential aberrations, as well as for…”
Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, positive): “…epigenetic memory, these technical attributes of incomplete reprogramming can be erased following additional Cell 143, November 12, 2010 ª2010 Elsevier Inc. 519 cell division or by supplementing other exogenous factors during reprogramming (Silva et al., 2009; Polo et al., 2010; Kim et al., 2010).”
The promise of induced pluripotent stem cells in research and therapy (2012, background): “In another comprehensive study, Polo and colleagues evaluated the effect of cellular origin on the gene-expression pattern, epigenetic properties and functional abilities of genetically matched mouse iPS cell”
Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging (2013, neutral): “…such as methylation levels at particular CpG sites that have been reported to predict donor age across multiple tissues (Hannum et al., 2013; Koch and Wagner, 2011) or methylation patterns reported to reflect epigenetic memory in iPSCs of donor cell fate (Kim et al., 2010; Polo et al., 2010).”
Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming (2012, neutral): “, 2010b) was initially thought to be restricted to low passage (<15) hiPSCs (Polo et al., 2010), but recent data suggest that this effect is maintained in later passages as well (Ohi et al.”
Control of Embryonic Stem Cell State (2011, background): “However, some iPSCs do retain an epigenetic memory of their donor cells (Kim et al., 2010b; Polo et al., 2010; Lister et al., 2011).”
Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. (2011, positive): “Recently, it has been shown that following the reprogramming of mouse iPSCs, an epigenetic memory is inherited from the parental cell (Kim et al., 2010; Polo et al., 2010).”