Jak kinase 3 signaling in microgliogenesis from the spinal nestin+ progenitors in both development and response to injury

Abstract

During spinal cord development, endogenous progenitors expressing nestin can migrate into the target and differentiate into neurons and other glial cells. Microglial cells can also be derived from nestin+ progenitor cells, even in the adult brain. Knockdown of Jak kinase 3 (Jak3) signaling can increase neurogenesis with longer neurite outgrowth in cortical progenitor cells. This study investigated the effect of Jak3 signaling on differentiation from nestin+ progenitor cells using E13.5 spinal progenitor cell cultures. In growth factors-enriched culture, developing neurons could not survive after several days and also a significant proportion of nestin-expressing cells transformed into ameboid Iba1+ microglial cells, which increased exponentially after 5 days. This microgliogenesis was predominantly regulated by Jak3 signaling, which was confirmed by transcription factors responsible for microgliogenesis, and microglial migration and phagocytosis, such as Pu.1, Irf8, and Runx1. Jak3 inhibition also significantly increased the Tuj1+ growing neurites with little microglial activation. These results indicated that neuronal and microglial cell differentiation was regulated primarily by Jak3 signaling and the developing neurons and neurite outgrowth might also be regulated by Jak3-dependent microglial activity.

Rat Spinal Cord Injury Associated with Spasticity Leads to Widespread Changes in the Regulation of Retained Introns

“…Interestingly, PU.1 (Spi-1 proto-oncogene) itself is deregulated during injury, suggesting it could be master-regulator of the injury response ( Supplementary Table S1 ). PU1 is implicated in myeloid maturation especially differentiation and activation of macrophages and cytokine regulation 30 , 31 and is increased three days after SCI in microglia. 15 …”

Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum

“…9B). Beside neurogenesis and activation of resting microglial, the present study also probed the concept of microgliogenesis in adult brain, a critical response in pathological conditions that has not been fully explored (Barua et al, 2017). We found a reduction in the number of new-born cells expressing Iba-1 (Iba1+/BrdU+ cells) in the SVZ of alcoholexposed rats that was not affected after OEA treatment.…”

Effect of Janus Kinase 3 Inhibitor on Sebaceous Gland Regeneration during Skin Wound Healing

“…In the regeneration of endothelium after vascular injury also, Jak3 can regulate the reendothelization following mechanical injury, which can modulate neointimal formation 33 . Jak3 can modulate myocardial injury by reducing inflammation-induced apoptotic damage 34 , and spinal cord injury can be regulated by participating transcriptional factors for microglial cell differentiation 35 .…”