Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience

Abstract

The scarcity of live human brain cells for experimental access has for a long time limited our ability to study complex human neurological disorders and elucidate basic neuroscientific mechanisms. A decade ago, the development of methods to reprogramme somatic human cells into induced pluripotent stem cells enabled the in vitro generation of a wide range of neural cells from virtually any human individual. The growth of methods to generate more robust and defined neural cell types through reprogramming and direct conversion into induced neurons has led to the establishment of various human reprogramming-based neural disease models.

Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration

“…Self-renewing and pluripotency features of human pluripotent stem cells (hPSCs) have greatly facilitated understanding of the developing human nervous system and the pathogenesis of various neurological disorders (Mertens et al, 2016). Since the first report of neural rosette formation from human embryonic stem cells (ESCs) (Zhang et al, 2001), techniques to derive neural cells from hPSCs have continuously evolved, such that now we readily generate neural tissues in vitro , that resemble the 3-dimensional (3-D) organization of various brain regions (Kelava and Lancaster, 2016; Lancaster and Knoblich, 2014).…”

Circadian clocks: from stem cells to tissue homeostasis and regeneration

“…In vitro , these cells proliferate indefinitely and can give rise to derivatives of all three germ layers (ecto‐, meso‐, and endoderm). Indeed, directed differentiation toward clinically relevant cell types such as neurons 7, hepatocytes 8, and cardiac cells 9 is common practice nowadays. Therefore, these cells hold great promise for disease modeling, drug development as well as cell‐based regenerative therapies.…”

Programming and reprogramming neural cell types using synthetic transcription factors

“…The timing, levels, duration and combination of many inductive cues determines the precise trajectory of differentiation. Detailed differentiation protocols have been developed for mouse embryonic stem cells, enabling differentiation to a range of specific lineages, including derivatives of all three major germ layers: reviewed in (Murry & Keller 2008); iPSCs (Mertens et al 2016) and NSCs (Massirer et al 2011;Glaser et al 2007). Lastly, differentiation process can be facilitated by overexpression of specific master regulators, a process termed forward programing.…”