instruction:
In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.
question:
Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in 90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives. Metabolic modulation compromises GTIC viability. Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results highlight the potential of hiPSCs for studying human tumourigenesis.
answer:
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells

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The Snail transcription factor plays a key role in regulating diverse developmental processes but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal, and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway because coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts via p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology.
answer:
Snail coordinately regulates downstream pathways to control multiple aspects of mammalian neural precursor development.

question:
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a fatal clinical disorder characterized by extracellular deposition of abnormal fibrils derived from misfolded, normally soluble transthyretin (TTR) molecules. The disease is most commonly caused by a point mutation within the TTR gene inherited in an autosomal dominant fashion. Over 100 of such mutations have been identified, leading to destabilization of the physiological TTR tetramer. As a result, many monomers originate with a tendency for spontaneous conformational changes and self-aggregation. The main clinical feature of TTR-FAP is progressive sensorimotor and autonomic neuropathy. In the beginning, this polyneuropathy predominantly involves small unmyelinated nerve fibers with the result of dissociated sensory loss disproportionately affecting sensation of pain and temperature. Autonomic neuropathy typically accompanies sensory deficits early in the disease course. The symptoms include orthostatic hypotension, constipation alternating with diarrhea, erectile dysfunction, anhydrosis, and urinary retention or incontinence. Later, involvement of motor fibers causes rapidly progressive weakness and gait disturbances. In addition to the peripheral nervous system, the heart and the gut are frequently affected. Onset of symptoms is bimodal, with one peak at age 33 years (early onset) and another distinct peak in the sixth decade of life (late onset). The course of TTR-FAP is uniformly progressive and fatal. Death occurs an average of 10.8 years after the onset of symptoms in Portuguese patients, and 7.3 years in late-onset Japanese patients. Common causes include cachexia, cardiac failure, arrhythmia, and secondary infections. Liver transplantation is the standard therapy for patients who are in a clinical condition good enough to tolerate this intervention because it stops progression of neuropathy by removing the main source of mutant TTR. Recently, orally administered tafamidis meglumine has been approved by European authorities for treatment of FAP. The substance has been shown to stabilize the TTR tetramer, thereby improving the outcome of patients with TTR-FAP. Various other strategies have been studied in vitro to prevent TTR amyloidosis, including gene therapy, immunization, dissolution of TTR aggregates, and free radical scavengers, but none of them is ready for clinical use so far.
answer:
Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis