Similar Datasets
Project description:Many developmental signaling pathways have been implicated in lineage-specific differentiation; however, mechanisms that explicitly control differentiation timing remain poorly defined in mammals. We report that murine Hedgehog signaling is a heterochronic pathway that determines the timing of progenitor differentiation. Hedgehog activity was necessary to prevent premature differentiation of second heart field (SHF) cardiac progenitors in mouse embryos, and the Hedgehog transcription factor GLI1 was sufficient to delay differentiation of cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro, akin to that of SHF progenitors in vivo, which prevented the onset of the cardiac differentiation program. A Hedgehog signaling-dependent active-to-repressive GLI transition functioned as a differentiation timer, restricting the progenitor network to the SHF. GLI1 expression was associated with progenitor status across germ layers, and it delayed the differentiation of neural progenitors in vitro, suggesting a broad role for Hedgehog signaling as a heterochronic pathway.
| S-EPMC10506397 | biostudies-literature
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196085 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196083 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196094 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196087 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196092 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196090 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196088 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE209921 | GEO
Project description:We report that Hedgehog signaling is a heterochronic pathway that determines the timing of the transition from specified cardiac progenitor to differentiated cardiomyocyte, a function distinct from its previously described roles affecting cellular patterning or proliferation. Hedgehog signaling was required to prevent premature differentiation and disruption of cardiac morphogenesis in vivo and the Hedgehog signaling transcription factor GLI1 was sufficient to delay differentiation in stem cell-derived cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro that inhibited the induction of the cardiac differentiation program. The GLI1-driven gene regulatory network is sufficient to induce Hedgehog-naive in vitro cardiac progenitors to adopt an epigenomic state reminiscent of second heart field cardiac progenitors in vivo. A Hh-dependent GLI transcription factor switch functions as a differentiation timer, restricting activity of the progenitor network to the second heart field and permitting cardiomyocyte differentiation in the heart. GLI1 expression is broadly associated with the progenitor state, and its activity also delayed the differentiation of specified neural progenitors in vitro. We posit that Hedgehog signaling functions as a heterochronic regulator that transiently maintains diverse progenitor populations for complex organ development and that may explain diverse Hedgehog signaling-dependent phenomena.
2022-08-03 | GSE196081 | GEO