Induced neuronal cells: how to make and define a neuron.
- Authors
- Yang, Nan; Ng, Yi Han; Pang, Zhiping P; Südhof, Thomas C; Wernig, Marius
- Year
- 2011
- Journal
- Cell stem cell
- PMID
- 22136927
- DOI
- 10.1016/j.stem.2011.11.015
- PMCID
- PMC4377331
Cellular plasticity is a major focus of investigation in developmental biology. The recent discovery that induced neuronal (iN) cells can be generated from mouse and human fibroblasts by expression of defined transcription factors suggested that cell fate plasticity is much wider than previously anticipated. In this review, we summarize the most recent developments in this nascent field and suggest criteria to help define and categorize iN cells that take into account the complexity of neuronal identity.
Summary of all iN cell studies to date
LLM interpretation
This diagram summarizes various studies on induced neuron (iN) cell conversion in mice and humans. It maps the starting cell types (hepatocytes and fibroblasts) to the specific transcription factor cocktails used to derive different neuronal subtypes, including excitatory neurons, NPCs, DA neurons, and motor neurons. Each pathway is linked to the corresponding research publications listed at the bottom of the figure.
Direct versus indirect reprogrammingLong expression of the 4 Yamanaka factors lead to iPS cell formation when grown in ES cell media. Short expression induces a transient, unstable pluripotent state that can be quickly differentiated into neural precursors or cardiomyocytes depending on the media components. Direct reprogramming (e.g. iN cell reprogramming) does not involve a pluripotent intermediate stage. Red arrows: reprogramming, grey arrows: differentiation.
LLM interpretation
This diagram illustrates the pathways for direct and indirect reprogramming of fibroblasts into neurons. Indirect reprogramming involves a transition through "Transient pluripotent cells" induced by the Yamanaka factors (Sox2, Oct4, Klf4, c-Myc), which can then differentiate into neural precursors (NPCs) and neurons using neural media, or into iPS cells using ES cell media. Direct reprogramming is shown as a direct transition from fibroblasts to neurons, bypassing the pluripotent intermediate stage.
Neuronal properties in order of stringency (maturation/ extent of reprogramming)Abbreviations: NT neurotransmitter, MAP2 microtubule associated protein 2
LLM interpretation
This figure is a summary table outlining the criteria for evaluating the degree of neuronal reprogramming, categorized by "Property" and "Specific criteria." The properties are organized by increasing stringency, transitioning from "Partially reprogrammed iN cells" (immature) to "Fully reprogrammed iN cells" (mature). The criteria range from basic morphology and marker expression to complex functional capabilities such as postsynaptic function and synaptic plasticity.
Examples of morphological and electrophysiological criteria of iN cellsA, Tuj1-positive fibroblasts extending one or more fairly thin cellular process. B, Immature iN cells extending one or two long branching neuritis from their soma. C, More mature iN cell morphologies characterized by multiple, long, branching processes extending from the cell body. Often iN cells sit on top of a dense network of neuritis derived from surrounding cells. D, A voltage clamp recording of spontaneous PSCs. The baseline is fairly tight and there is only little noise detectable. Both clusters of spikes (region 1, black) and separated spikes (region 2, red) represent most likely postsynaptic events as seen by higher time resolution (lower black and red traces). PSCs are typically of asymmetric shape with a fast deviation from the baseline followed by a slow rectification. E, A trace in the same recording mode with a much noisier baseline. Region 1 shows a group of spikes with similar amplitude deviation as in D. Higher resolution (lower black trace) reveals high levels of baseline fluctuation precluding the identification of PSCs. Other areas in the same trace (e.g. region 2, red trace) contain spikes that most likely represent synaptic currents.
LLM interpretation
This figure presents morphological and electrophysiological characterizations of induced neurons (iN cells). Panels A, B, and C show fluorescence microscopy images of Tuj1-positive cells, progressing from fibroblasts with thin processes to mature neurons with multiple long, branching neurites. Panels D and E display voltage clamp recordings of spontaneous postsynaptic currents (PSCs), with high-resolution insets (regions 1 and 2) comparing a clean baseline with identifiable asymmetric PSCs (D) against a noisy baseline that precludes PSC identification (E).
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