In Vivo Organ Regeneration via Stroma-Dependent Adult Lineage Reprogramming
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PROVIDER: PRJNA159423 | ENA |
REPOSITORIES: ENA
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Project description:Remarkable progress has been made in cell fate reprogramming by forced expression of a small number of transcription factors. Major challenges remain, however, in regenerative medicine regarding how to target multiple cell types and direct them to form a functional organ in vivo. Here, we demonstrate that, by changing their stromal microenvironment, adult differentiated cells of endodermal origin can be reprogrammed to generate a functional ectodermal organ. The process of organ regeneration is highly efficient and complete, and depends on epithelial-stromal interactions that lead to successful remodeling of the extracellular matrix and stromal cells that are essential for organ function. Furthermore, it is a multistep process consisting of changes in cell fate, where dedifferentiation occurs more rapidly than redifferentiation, and subsequent morphogenetic reprogramming. Remarkably, neither direct transdifferentiation nor a complete reversion to the pluripotency state is involved in the reprogramming process; instead it features dynamic activities of essential genes that regulate pluripotency and lineage development. Our data have important implications for stem cell biology, cancer biology, and regenerative medicine.
2021-12-31 | GSE37308 | GEO
Project description:Remarkable progress has been made in cell fate reprogramming by forced expression of a small number of transcription factors. Major challenges remain, however, in regenerative medicine regarding how to target multiple cell types and direct them to form a functional organ in vivo. Here, we demonstrate that, by changing their stromal microenvironment, adult differentiated cells of endodermal origin can be reprogrammed to generate a functional ectodermal organ. The process of organ regeneration is highly efficient and complete, and depends on epithelial-stromal interactions that lead to successful remodeling of the extracellular matrix and stromal cells that are essential for organ function. Furthermore, it is a multistep process consisting of changes in cell fate, where dedifferentiation occurs more rapidly than redifferentiation, and subsequent morphogenetic reprogramming. Remarkably, neither direct transdifferentiation nor a complete reversion to the pluripotency state is involved in the reprogramming process; instead it features dynamic activities of essential genes that regulate pluripotency and lineage development. Our data have important implications for stem cell biology, cancer biology, and regenerative medicine.
2021-12-31 | GSE37289 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-31 | GSE37309 | GEO
Project description:Hedgehog gradient in the stroma maintains niche diversity and organ function
| PRJNA398101 | ENA
Project description:A critical step in regeneration is recreating the cellular identities and patterns of lost organs long after embryogenesis is complete. In plants, perpetual (indeterminate) organ growth occurs in apical stem cell niches, which have been shown to re-establish quickly when damaged or removed (1,2). Here we ask whether the machinery of perpetual organ growth, stem cell activity, is needed for the phase of regeneration that leads to replenishing lost cell identities and patterning, or, whether organ re-establishment enlists a wider group of pluripotent cells. We adapt a root tip regeneration system to Arabidopsis that permits us to assess the molecular and functional recovery of specific cell fates during organ regeneration. These results suggest a rapid restoration of missing cell fate and function in advance of the recovery of stem cell activity. Surprisingly, plants with mutations that fail to maintain stem cell activity were able to re-pattern their distal tip and re-specify lost cell fates. Thus, although stem cell activity is required to resume indeterminate growth (3), our results show it is not necessary for cell re-specification and patterning steps. This implies a regeneration mechanism that coordinates patterning of the whole organ, as in embryogenesis, but is initiated from different starting morphologies. 1. Feldman, L. J. Denovo Origin of Quiescent Center Regenerating Root Apices of Zea-Mays. Planta 128, 207-212 (1976). 2. Xu, J. et al. A molecular framework for plant regeneration. Science 311, 385-8 (2006). 3. Gordon, S. P. et al. Pattern formation during de novo assembly of the Arabidopsis shoot meristem. Development 134, 3539-48 (2007). We adapted root tip excision techniques to Arabidopsis, enabling us to perform microarray profiling of regenerating root tissue. Excisions were performed at 4 days post-germination (dpg) at a distance of 130 um from the root tip, resulting in the complete excision of QC, all surrounding stem cells along with several tiers of daughter cells, and the root cap, including all of the columella and most of the lateral root cap. The tip section and then approximately 70 um of regenerating tissue was recut at different time points post cutting. We sampled regenerating stumps at 0hrs, 5 hrs, 13 hrs, 22 hrs, and 7 days after the excision for microarray analysis (Methods). We also sampled root sections immediately above the zone competent to regenerate at 270 um to approximately 340 um. Experiment Overall Design: 30 samples with 4 or 3 replicates for each condition representing a time course of regenerating root stumps and including controls for root tips (regeneration endpoint) at 4 dpg and 8 dpg and a wounded set of samples representing root tissue at 270-340 mm from the root tip for non-regeneration control
2008-11-13 | E-GEOD-9996 | biostudies-arrayexpress
Project description:A critical step in regeneration is recreating the cellular identities and patterns of lost organs long after embryogenesis is complete. In plants, perpetual (indeterminate) organ growth occurs in apical stem cell niches, which have been shown to re-establish quickly when damaged or removed (1,2). Here we ask whether the machinery of perpetual organ growth, stem cell activity, is needed for the phase of regeneration that leads to replenishing lost cell identities and patterning, or, whether organ re-establishment enlists a wider group of pluripotent cells. We adapt a root tip regeneration system to Arabidopsis that permits us to assess the molecular and functional recovery of specific cell fates during organ regeneration. These results suggest a rapid restoration of missing cell fate and function in advance of the recovery of stem cell activity. Surprisingly, plants with mutations that fail to maintain stem cell activity were able to re-pattern their distal tip and re-specify lost cell fates. Thus, although stem cell activity is required to resume indeterminate growth (3), our results show it is not necessary for cell re-specification and patterning steps. This implies a regeneration mechanism that coordinates patterning of the whole organ, as in embryogenesis, but is initiated from different starting morphologies. 1. Feldman, L. J. Denovo Origin of Quiescent Center Regenerating Root Apices of Zea-Mays. Planta 128, 207-212 (1976). 2. Xu, J. et al. A molecular framework for plant regeneration. Science 311, 385-8 (2006). 3. Gordon, S. P. et al. Pattern formation during de novo assembly of the Arabidopsis shoot meristem. Development 134, 3539-48 (2007). We adapted root tip excision techniques to Arabidopsis, enabling us to perform microarray profiling of regenerating root tissue. Excisions were performed at 4 days post-germination (dpg) at a distance of 130 um from the root tip, resulting in the complete excision of QC, all surrounding stem cells along with several tiers of daughter cells, and the root cap, including all of the columella and most of the lateral root cap. The tip section and then approximately 70 um of regenerating tissue was recut at different time points post cutting. We sampled regenerating stumps at 0hrs, 5 hrs, 13 hrs, 22 hrs, and 7 days after the excision for microarray analysis (Methods). We also sampled root sections immediately above the zone competent to regenerate at 270 um to approximately 340 um. Keywords: time course, development, root regeneration
2008-10-30 | GSE9996 | GEO
Project description:Genomic reprogramming and cellular dedifferentiation are critical to the success of de novo tissue regeneration in lower vertebrates such as zebrafish and axolotl. ChIP-seq of the histone modifications H3K27Ac, H3K27me3, and H3K4me3 was used to characterize early epigenetic changes in a zebrafish in vivo model of adult muscle regeneration.
2019-12-06 | GSE137304 | GEO
Project description:Hedgehog gradient in the stroma maintains niche diversity and organ function [scRNA-seq]
| PRJNA423037 | ENA
Project description:Mammalian tissues have a limited regenerative capacity. Previous studies showed that dedifferentiation contributes to tissue regeneration in non-mammalian vertebrate species such as zebrafish and newt. However, dedifferentiation is rarely observed in mammalian tissues even in the neonatal stage and therefore artificial induction of dedifferentiation might enhance regeneration in mammalian tissues. Here we demonstrate that short-term expression of Yamanaka 4 factors (4F) induces dedifferentiation and proliferation in the liver by using lineage-traceable, hepatocyte-specific 4F inducible mouse model. Global transcriptome analysis shows that 4F expression transiently reduces the expression of hepatic-lineage markers and induces the expression of a large set of proliferative markers and epigenetic modifiers along with global epigenetic changes as assessed by DNA-accessibility analysis. More importantly, lineage-tracing experiments showed that 4F-expressing hepatocytes acquire liver stem/progenitor cell markers, suggesting that 4F induces partial reprogramming. Moreover, 4F enhances MyoD-mediated transdifferentiation in the liver, suggesting that 4F endows hepatocytes with plasticity. Lastly, 4F expression attenuated liver injury associated with more proliferative capacity and better survival rate, indicating that 4F enhances liver regeneration. Taken together, these results demonstrate that liver-specific 4F expression induces dedifferentiation and promotes liver regeneration.
2022-04-27 | GSE144600 | GEO
Project description:Transient epigenetic reprogramming during adult zebrafish muscle regeneration
| PRJNA565138 | ENA