See how a stem cell differentiates… up close and in 3D

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The maturation of stem cells into various lineages has been studied extensively as the central feature of the therapeutic potential of stem cells in regenerative medicine. The commitment of a stem cells to a mature cell type is accompanied by epigenetic changes of the cell’s genetic makeup. Until now, studies of those events has uncovered a lot of information about the nature of the rearrangement of genes specific for the control of the cell’s specific state prior and during differentiation. The suggestion is that these rearrangements lead to 3D distribution of chromatin in vivo.

Now, advances in in high-resolution imaging have allowed for an unprecedented view into the 3D architecture of chromatin during cell maturation. A study, by  the lab of Dr. Carolyn Larabell, from the Department of Anatomy at the University of California San Francisco and the Physical Biosciences Division at Lawrence Berkeley National Laboratory, reported on the use of soft X-ray tomography as a tool for the visualization of genetic changes during stem cell differentiation.

Soft x-ray tomography had previously been used to demonstrate high-resolution, 3D imaging of human stem cells, where it allowed the visualization of all major organelles at 50 nm spatial resolution.

Using the technique, the authors have been able to resolve the biophysical state and the conformation of the genome with high spatial precision during cell differentiation, feats that had been unachievable previously.

In the paper, titled “Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo,” the authors imaged three cell types of the olfactory epithelium, horizontal basal cells (HBCs), globose basal cells (GBCs), and mature olfactory sensory neurons (mOSNs). Thesse cells were selected as they could be appropriated as multipotent stem cells, neuronal progenitors, and terminally differentiated neurons, respectively.

During differentiation, chromatin undergoes reorganization and compaction, moving from a multi-potent state to a differentiated, mature state. During those stages, the authors also observed the relocation of chromatin from the periphery of the nucleus, where it is mainly located in stem cells, to the nuclear core in mature neurons.

 

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Reorganization of cells from mouse olfactory epithelium—multipotent stem cell, neuronal progenitor cell, and mature olfactory sensory neuron—during differentiation. Heterochromatin (blue), euchromatin (green), and mitochondria (copper). Figure from Le Gros et al., 2016.

 

Beyond the remarkable high-resolution details, the study demonstrated that soft x-ray tomography is a powerful tool for the study of the genetic architecture during cellular differentiation in vivo.

Read the entire article here.

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