The HNPCs were initially obtained from first-trimester human embryonic forebrain tissue and can be long term expanded into high numbers in vitro [ 42] maintaining the capacity to form neurons, astrocytes, or oligodendrocytes, the three main phenotypes in the CNS [ 32].
With the exception of AML 2005-289, long-term expanding cocultures could be established reaching 4- to 25-fold expansion, after 4 weeks of culture.
In conclusion, these data indicated that the long-term expanding pancreas organoid cultures derive from duct cells.
In 79% (15/19) of the tested AML cases, long-term expanding cocultures could be generated (Fig. 2a, b).
Using this Tsc1 conditional knockout mouse model, the group established long-term expanding postnatal NSC lines derived from the subventricular zone.
To assess the role of mTOR pathway hyperactivation in postnatal SVZ NSCs ex vivo, we established long-term expanding NSC lines at P7.
With respect to the NEP-targeted mouse model in which Tsc1 loss postnatally was restricted to the dorsolateral corner of the SVZ, the Tsc1 c/− /hGFAP2-Cre+ mutant mouse carries the relevant advantage of deleting Tsc1 in the whole SVZ region, thus allowing the establishment of long-term expanding postnatal mutant NSC lines.
Meanwhile, Zhang et al. demonstrated that fibroblasts could be induced into expandable iCPCs by the CASD lineage conversion strategy and these iCPCs could be further long-term expanded using a combination of growth factors and small molecules (BMP4, Activin A, CHIR99021 and SU5402) (Zhang et al., 2016b).
However, chromosomal rearrangements have been detected in long-term expanded adult murine NSCs which apparently do not result in a malignant phenotype [2].
This restricted transcriptional code resulted in both glutamatergic and GABAergic neurotransmitter phenotypes from these regions which contrasts with the preferential GABAergic phenotype seen in long-term expanded primary and ES cell derived neural precursors [71], [72].
We show here that exposure of long-term expanded hNSCs isolated from the developing human brain to defined combinations of pro-oligodendroglial factors results in the generation of large numbers of oligodendroglial cells at the early stages of lineage commitment/differentiation.
