The BCL-2 family controls stem cell identity by regulating mitochondrial dynamics and priming

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Summary Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity and lineage commitment. Our preliminary studies suggest an emerging landscape in which the BCL-2 family of proteins has an active role in maintaining cell identity independently of its role in mitochondrial outer permeabilization. We will employ a multidisciplinary approach combining molecular biology, biochemistry, genetics, and cell biology to address fundamental questions such as: What are the signaling events involved in the role of BCL-2 family maintaining a fragmented mitochondrial network in stem cells independently of its role in apoptosis? Are mitochondrial dynamics mediated through the BCL-2 family a requirement for cellular reprogramming? What are the signaling mechanisms involved in translating the information from the mitochondria into the nucleus to ultimately modulate cell fate? We plan to combine our expertise in mitochondrial and stem cell biology with state-of- the-art approaches to seek answers to these questions and reveal novel functions of the BCL-2 family in stem cell identity and commitment.