The transcription factor Tbx3 fosters regeneration from acute pancreatitis and shows switching expression patterns in the embryonic pancreas

Introduction Re-activation of genetic programs from early development is vital for injury-induced organ regeneration. Tissue resident stem cells share features of pluripotent stem cells such as differentiation potential and self-renewal capacity and act as major source of organ regeneration. T-Box Transcription Factor 3 (Tbx3) facilitates somatic reprogramming of adult cells into induced pluripotent stem cells and act as a dynamic switch in activation of pluripotency, and thus stem cell renewal.

Aims Therefore, we hypothesize that Tbx3 is expressed during and involved in embryonic development of the pancreas and further enhances regeneration from experimentally induced acute pancreatitis due to the control of tissue stem cell related self-renewal capacity.

Results Performing immunofluorescence studies on embryonic mice from a Tbx3-Venus reporter mouse strain, we demonstrate that Tbx3 expression is

• augmented at different stages during embryonic development of the pancreas,

• switches expression patterns from mesenchymal to epithelial expression and

• is absent in adult pancreas.

However, pancreas specific deletion of Tbx3 already at embryonic stage using a p48-Cre mouse line did not show any phenotypic alterations in the adult pancreas compared to wildtype counterparts. Interestingly, induction of experimental acute pancreatitis by caerulein led to an upregulation of Tbx3 expression during the regeneration phase in wildtype mice. Concordant with our hypothesis, we observed a delayed pancreatic regeneration after caerulein-induced acute pancreatitis in p48-Cre depleted homozygous Tbx3 knockout mice, resulting in a higher rate of acinar-ductal-metaplasias and damaged pancreatic area.

Conclusion Taken together, we observed differential Tbx3 expression during embryonic development and again during acute pancreatitis. A knockout of Tbx3 leads to delayed organ regeneration after induced damage. This may indicate that Tbx3 favors tissue development and repair through regulation of stem cell compartments.

Publication History

Article published online:
07 September 2021