A Dynamic Role of TBX3 in the Pluripotency Circuitry

•Tbx3 is not required for induction and maintenance of pluripotency•Tbx3 is heterogeneously expressed in pluripotent cell in vivo and in vitro•In vivo Tbx3-high cells are committed to the PE; low cells commit to the epiblast•Loss of Tbx3 leads to complex compensational processes in pluripotent stem cells

SummaryPluripotency represents a cell state comprising a fine-tuned pattern of transcription factor activity required for embryonic stem cell (ESC) self-renewal. TBX3 is the earliest expressed member of the T-box transcription factor family and is involved in maintenance and induction of pluripotency. Hence, TBX3 is believed to be a key member of the pluripotency circuitry, with loss of TBX3 coinciding with loss of pluripotency. We report a dynamic expression of TBX3 in vitro and in vivo using genetic reporter tools tracking TBX3 expression in mouse ESCs (mESCs). Low TBX3 levels are associated with reduced pluripotency, resembling the more mature epiblast. Notably, TBX3-low cells maintain the intrinsic capability to switch to a TBX3-high state and vice versa. Additionally, we show TBX3 to be dispensable for induction and maintenance of naive pluripotency as well as for germ cell development. These data highlight novel facets of TBX3 action in mESCs.

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