ABSTRACT
The transcription factor Ascl1 can reprogram fibroblasts,astrocytes,Muller glial cells and other somatic cells in-to multiple subtypes of induced neurons,including dopaminergic neurons,amino acid neurons,etc.The complex mechanism in-volved in this process includes hierarchical mechanism and changes in transcription level.This article reviews the research on re-programming of somatic cell into neurons induced by Ascl1.
ABSTRACT
Abstract Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete‐scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.
ABSTRACT
Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1
ABSTRACT
Objective:ASCL-1 gene expression is closely related to pulmonary neuroendocrine (NE) tumors, such as small cell carcino-ma, atypical carcinoid, carcinoid, and large cell NE carcinoma. This study aimed to analyze ASCL-1 protein expression in lung adenocar-cinoma (AD) and its correlation with prognosis. Methods:ASCL-1 protein expression in 283 cases of AD was determined through immu-nohistochemical analysis and compared with the expression of traditional NE markers, including chromogranin A, CD56, and synapto-physin. Western blot was performed to detect the ASCL-1 protein expression levels in AD. Single factor Chi-square test and Logistic multiple factor regression analysis were conducted to explore the factors related to ASCL-1 expression. Kaplan-Meier survival analysis was applied to evaluate the prognosis of patients with AD. Results:Immunohistochemical analysis showed that ASCL-1 expression was positive in 48/283 (16.9%) AD and positively correlated with NE markers (0<r<1, P<0.05). Western blot revealed that ASCL-1 protein was expressed in 63 cases of AD, in their tumor-adjacent normal samples, and in 9 cases of AD. By contrast, this protein was not ex-pressed in tumor-adjacent normal tissues. Single factor Chi-square test and multivariate logistic regression analysis indicated that AS-CL-1 protein expression was associated with smoking, tumor differentiation, TNM staging, and lymph node metastasis. Kaplan-Meier survival analysis demonstrated that overall survival (OS) time was shorter in the ASCL-1-positive group than in the ASCL-1-negative group (P<0.05). Conclusion:ASCL-1 protein expression may serve as an independent prognostic factor for patients with lung AD.