Direct Conversion to Achieve Glial Cell Fates: Oligodendrocytes and Schwann Cells

Abstract

Glia have been known for its pivotal roles in physiological and pathological conditions in the nervous system. To study glial biology, multiple approaches have been applied to utilize glial cells for research, including stem cell-based technologies. Human glial cells differentiated from pluripotent stem cells are now available, allowing us to study the structural and functional roles of glia in the nervous system, although the efficiency is still low. Direct conversion is an advanced strategy governing fate conversion of diverse cell types directly into the desired lineage. This novel strategy stands as a promising approach for preliminary research and regenerative medicine. Direct conversion employs genetic and environmental cues to change cell fate to that with the required functional cell properties while retaining maturity-related molecular features. As an alternative method, it is now possible to obtain a variety of mature cell populations that could not be obtained using conventional differentiation methods. This review summarizes current achievements in obtaining glia, particularly oligodendrocytes and Schwann cells.

Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion

“…However, our study has limitations of oversimplifying the complex interaction between developing immature gut and differentiating peripheral neurons. The enteric nervous system in the colon is composed of various types of neurons and enteric glial cells ( 36 ), forming complex neural networks in the submucosal and myenteric plexuses ( 37 ). To clarify the impact of interactions between immature organoids and developing neurons on the functional maturation of the gut epithelium and the functional specification of neural cells, it is necessary to differentiate the various types of neural cell constituents and conduct further investigations into the precise mechanisms underlying nonsynaptic transmission of substance P.…”

Development and In Vitro Differentiation of Schwann Cells

“…Besides embryonic, induced, or adult tissue-derived stem cells, in vitro Schwann cell differentiation has used human [ 119 , 177 , 224 , 225 , 226 , 227 , 228 ] and rodent [ 177 , 223 ] skin fibroblasts via direct conversion methods, bypassing the pluripotency stage (reviewed by Yun et al, 2022 [ 283 ]). In most studies, conversion of fibroblasts was achieved by introducing transcription factors driving neural crest and/or Schwann cell fate, mostly Sox10 [ 119 , 227 ] in combination with Krox20 (also known as Egr2) [ 177 , 226 ], and subsequent culture in Schwann cell differentiation medium containing combinations of Nrg1, forskolin, PDGF, db-cAMP, CNTF, bFGF, and FBS.…”

Understanding the cellular pathogenesis of COVID-19 symptoms using organoid technology

“…Although a transgenic mouse model expressing human ACE2 indicated that SARS-CoV-2 infection occurred only in epithelial cells, not olfactory neurons [30], the results of the direct infection of hPSC-derived peripheral neurons with SARS-CoV-2 [31], along with autopsy data [26,79,80], still presents a potential nerve track for viral spread through synaptic transmission. In order to overcome the limitations of animal or cell-based research, studies using mature brain organoids with the concept of a neuronal assembloid are required in the near future [71,81,82].…”