In vivo chemical reprogramming of astrocytes into neurons

Abstract

In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram astrocytes into neurons. The in situ chemically induced neurons resemble endogenous neurons in terms of neuron-specific marker expression, electrophysiological properties, and synaptic connectivity. Our study demonstrates the feasibility of in vivo chemical reprogramming in the adult mouse brain and provides a potential approach for developing neuronal replacement therapies.

Small‐molecule‐driven direct reprogramming of Müller cells into bipolar‐like cells

“…11 In addition, small-molecule-driven reprogramming targeting these TFs has also been developed and applied in CNS. 12 Müller cells in retina and astrocytes in CNS have many features in common, such as their origins, functions, and stem cell characteristics. 13,14 In the retinal injury site of Zebrafish, Müller cells de-differentiate rapidly, proliferate, generate new neural stem cells, migrate to the damaged site, and eventually differentiate into neurons.…”

Neurovascular Reactivity in Tissue Scarring Following Cerebral Ischemia

“…While the cellular and molecular remodeling governing scarring at the injury site in the early phases could be beneficial by limiting neuroinflammation and excitotoxicity, degradation of ECM deposits in the chromic phase enables tissue plasticity. The promotion of neuroprotective astrocyte phenotypes through the use of biomaterials (147) or direct astrocyte reprogramming (148,149), as well as the functional reprogramming of PDGFRβ+ mural cells (150,151) may be promising strategies to enhance matrix degradation or neuronal repopulation in chronic stages post-ischemia to favor the formation of new functional cell networks.…”

Diverse biological and engineering strategies towards organ regeneration

“…Small molecules feature multiple targets, easy delivery, scalable doses and timing, and low immunogenicity, therefore they are popularly applied to the study of biological processes including cellular reprogramming. Hongkui Deng (Peking University, Beijing) presented their exciting work on the in situ transdifferentiation of astrocytes into neurons by small molecules (Ma et al 2021).…”