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Mitochondrial heterogeneity in human embryonic stem cell differentiation

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Pluripotent stem cells possess (PSCs) indefinite self-renewal and diverse differentiation abilities, making them an attractive source for applications in regenerative medicine. While significant progress has been made in generating several cell types in vitro, robust production of differentiated derivatives remains a challenge till date. This is attributed to the heterogeneous nature of PSCs, which results in differences in self-renewal and lineage restriction potential. Mitochondrial energy metabolism, biogenesis and dynamics impact stem cell identity and fate decisions. Genetic manipulation of mitochondrial proteins associated with mitochondrial metabolism and dynamics in the pluripotent state alters mitochondrial metabolism and differentiation propensity. Existence of metabolic states in an unperturbed hPSC cell compartment is unexplored. We are trying to unravel the molecular basis of this heterogeneity, which could be critical for identifying and controlling transitions in pluripotent populations.

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