> Axolotls, they discovered, have an ultra-sensitive version of mTOR, a molecule that acts as an on-off switch for protein production. And, like survivalists who fill their basements with non-perishable food for hard times, axolotl cells stockpile messenger RNA molecules, which contain genetic instructions for producing proteins. The combination of an easily activated mTOR molecule and a repository of ready-to-use mRNAs means that after an injury, axolotl cells can quickly produce the proteins needed for tissue regeneration.
> Abstract: Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these “induced ONL (iONL)” cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in MG in vivo, without retinal injury, mostly generates iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that coexpression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.
>> Is it possible to produce or convert Müller glial cells with Nanotransfection (stroma reprogramming), too?
> A number of factors have been identified as the important regulators in Müller glial cell reprogramming. The early response of Müller glial cells upon acute retinal injury, such as the regulation in the exit from quiescent state, the initiation of reactive gliosis, and the re-entry of cell cycle of Müller glial cells, displays significant difference between mouse and zebrafish, which may be mediated by the diverse regulation of Notch and TGFβ (transforming growth factor-β) isoforms and different chromatin accessibility.
> In a paper published in Nature Materials, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) report the development of a new hydrogel ink infused with gelatin fibers that enables 3D printing of a functional heart ventricle that mimics beating like a human heart. They discovered the fiber-infused gel (FIG) ink allows heart muscle cells printed in the shape of a ventricle to align and beat in coordination like a human heart chamber.
> “People have been trying to replicate organ structures and functions to test drug safety and efficacy as a way of predicting what might happen in the clinical setting,” says Suji Choi, research associate at SEAS and first author on the paper. But until now, 3D printing techniques alone have not been able to achieve physiologically-relevant alignment of cardiomyocytes, the cells responsible for transmitting electrical signals in a coordinated fashion to contract heart muscle.
> Axolotls, they discovered, have an ultra-sensitive version of mTOR, a molecule that acts as an on-off switch for protein production. And, like survivalists who fill their basements with non-perishable food for hard times, axolotl cells stockpile messenger RNA molecules, which contain genetic instructions for producing proteins. The combination of an easily activated mTOR molecule and a repository of ready-to-use mRNAs means that after an injury, axolotl cells can quickly produce the proteins needed for tissue regeneration.
From "Reactivating Dormant Cells in the Retina Brings New Hope for Vision Regeneration" (2023) https://news.ycombinator.com/item?id=35871887 :
> "Direct neuronal reprogramming by temporal identity factors" (2023) https://www.pnas.org/doi/10.1073/pnas.2122168120#abstract :
> Abstract: Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these “induced ONL (iONL)” cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in MG in vivo, without retinal injury, mostly generates iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that coexpression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.
>> Is it possible to produce or convert Müller glial cells with Nanotransfection (stroma reprogramming), too?
Muller glial cells and mTOR: https://scholar.google.com/scholar?hl=en&as_sdt=0%2C43&as_vi... :
- "Genetic and epigenetic regulators of retinal Müller glial cell reprogramming" (2023) https://www.sciencedirect.com/science/article/pii/S266737622... :
> A number of factors have been identified as the important regulators in Müller glial cell reprogramming. The early response of Müller glial cells upon acute retinal injury, such as the regulation in the exit from quiescent state, the initiation of reactive gliosis, and the re-entry of cell cycle of Müller glial cells, displays significant difference between mouse and zebrafish, which may be mediated by the diverse regulation of Notch and TGFβ (transforming growth factor-β) isoforms and different chromatin accessibility.
From "Fiber-infused ink enables 3D-printed heart muscle to beat" (2023) https://news.ycombinator.com/item?id=36894749 https://seas.harvard.edu/news/2023/07/fiber-infused-ink-enab... :
> In a paper published in Nature Materials, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) report the development of a new hydrogel ink infused with gelatin fibers that enables 3D printing of a functional heart ventricle that mimics beating like a human heart. They discovered the fiber-infused gel (FIG) ink allows heart muscle cells printed in the shape of a ventricle to align and beat in coordination like a human heart chamber.
> “People have been trying to replicate organ structures and functions to test drug safety and efficacy as a way of predicting what might happen in the clinical setting,” says Suji Choi, research associate at SEAS and first author on the paper. But until now, 3D printing techniques alone have not been able to achieve physiologically-relevant alignment of cardiomyocytes, the cells responsible for transmitting electrical signals in a coordinated fashion to contract heart muscle.
Hydrogel and gelatin.
Regenerative medicine: https://en.wikipedia.org/wiki/Regenerative_medicine
Regeneration in humans > Induced regeneration: https://en.wikipedia.org/wiki/Regeneration_in_humans#Induced...