APLNR marks a multipotent human cardiac progenitor derived with induced pluripotent stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE174335 | GEO | 2023/08/17
REPOSITORIES: GEO
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Project description:Efficient generation of functional cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) is critical for their use in regenerative medicine and other applications. In this study, we evaluated the effect of space microgravity (µg) on the differentiation of hiPSC-derived cardiac progenitors compared with parallel 1g condition on the International Space Station. Cryopreserved 3D cardiac progenitors derived from hiPSCs were cultured for 3 weeks. Compared with 1g culture, the µg culture had larger sphere sizes, increased expression of proliferation markers, higher counts of nuclei, and higher cell viability. Highly enriched cardiomyocytes generated in µg had appropriate gene expression and cardiac structure as well as improved function including contractility and Ca2+ handling. RNA-seq analysis of 3-day cultures revealed that short-term exposure of cardiac progenitor spheres to space microgravity upregulated genes involved in cell proliferation, cardiac differentiation, and contraction. These results indicate that space microgravity increased survival and proliferation of hiPSC-CMs and improved their structures and functions.
2022-09-08 | GSE188793 | GEO
Project description:Transcriptional profiling of 50% epiboly zebrafish embryos comparing wildtype (control) to Aplnra/b morpholino injected embryos. Goal was to determine any gene expression changes in embryos deficient for the Apelin receptor. Publication summary: The Apelin receptor (Aplnr) has been shown to be essential for proper cardiac progenitor migration during gastrulation. Loss of the Aplnr results in a delay in the ingression of lateral marginal cells and the complete absence of the heart and early cardiac gene expression. How the Aplnr is required at a molecular level for cardiac progenitor migration remains completely unknown. We present evidence to suggest that the Aplnr enhances Nodal signaling to initiate the migration program at the correct time in development. Apelin receptor loss of function embryos exhibit a reduction in a wide range of Nodal target genes while activation of the receptor is capable of boosting their expression. Furthermore, Aplnr deficient embryos are exquisitely sensitive to Nodal receptor inhibitors. In order to directly interrogate the functional consequence of reduced Nodal signaling in the Aplnr cardiac phenotype, we raised the level of Nodal activity in aplnr mutants and found that this was able to provide a near complete rescue. We next sought to determine a mechanism by which lower Nodal signaling levels could translate into a delay in migration. Remarkably, we observe a delay in the expression of mesp family members in Aplnr loss of function embryos at the beginning of gastrulation. The mesp family has previously been implicated in mesodermal migration and we show that they are downstream targets of Nodal. We propose that in the absence of the Aplnr the appropriate Nodal threshold required to initiate the downstream cardiac progenitor “specification/migration” program requires a longer length of time to be attained. This translates into a delay in migration and consequently cardiac progenitors are not capable of reaching their final destination. In this study we demonstrate how the fine tuning of a key signaling pathway is critical for the proper development of the early embryo.
2016-04-29 | GSE58683 | GEO
Project description:Previously, we reported upregulation of cardiac proliferation in cardiac progenitors derived from human induced pluripotent stem cells (hiPSC-CPCs) that were exposed to space microgravity for 3 days. The overall objective of this investigation was to understand how long-term exposure to microgravity affects the expansion and differentiation of hiPSC-CPCs. Cryopreserved cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) were exposed to space microgravity for 3 weeks in the International Space Station (ISS) and retrieved for transcriptomic profiling. RNA-seq analysis and gene ontology analysis revealed upregulation of cardiac tissue function and morphological terms while downregulating inflammation and ECM regulation terms. Upregulation of genes associated with cell cycle regulation and proliferation were notable as well. Combined with previous work, these results suggest that space microgravity improved cardiac differentiation and structure formation and potentially, proliferation.
2023-12-04 | GSE228063 | GEO
Project description:A hESC MESP1-MCHERRY reporter line was used to isolate and study the molecular character of MESP1 expressing pre-cardiac progenitors, derived from hESC. MESP1 is a key-transcription factor for pre-cardiac mesoderm and is marking the progenitor for almost all cells of the heart. This reporter line was used to study cardiac differentiation and the derivation of early cardiac progenitors in vitro. hESCs were differentiated towards the cardiac lineage, expressing MESP1-mCherry at day 3 of differentiation. Total RNA obtained from isolated MESP1-mCherry expressing progenitors was compared to that of non-MESP1-expressing progenitors and undifferentiated hESCs in order to characterize MESP1-specific transcription factors and proteins.
2014-09-01 | E-GEOD-56721 | biostudies-arrayexpress
Project description:The ability to differentiate human induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseases in vitro. The mechanisms underlying the specification of these cell types during human development are not well-understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA sequencing data revealed differential ETV2 dynamics in the two lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on the in vitro differentiation dynamics of two important cardiac lineages.
2023-01-20 | GSE157954 | GEO
Project description:The ability to differentiate human induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseases in vitro. The mechanisms underlying the specification of these cell types during human development are not well-understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA sequencing data revealed differential ETV2 dynamics in the two lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on the in vitro differentiation dynamics of two important cardiac lineages.
2023-01-20 | GSE202901 | 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 | 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 | 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