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Gama, V.

Publications and source records attributed to Gama, V..

3 recordsLinked to original sources

Spin{infty} an improved miniaturized spinning bioreactor for the generation of human cerebral organoids from pluripotent stem cells

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have become a powerful system to study early development events and to model human disease. Cerebral organoids are generally produced in static culture or in a culture vessel with active mixing, and the two most widely used systems for mixing are a large spinning flask and a miniaturized multi-well spinning bioreactor (also known as Spin Omega (Spin{Omega})). The Spin{Omega} provides a system that is amenable to drug testing, has increased throughput and reproducibility, and utilizes less culture media. However, technical limitations of this system include poor stability of select components and an elevated risk of contamination due to the inability to sterilize the device preassembled. Here, we report a new design of the miniaturized bioreactor system, which we term Spin{infty} that overcomes these concerns to permit long-term experiments.

bioengineering

Precise tuning of cortical contractility regulates cell shape during cytokinesis

The mechanical properties of the cellular cortex regulate shape changes during cell division, cell migration and tissue morphogenesis. During cell division, contractile force generated by the molecular motor myosin II (MII) at the equatorial cortex drives cleavage furrow ingression. Cleavage furrow ingression in turn increases stresses at the polar cortex, where contractility must be regulated to maintain cell shape during cytokinesis. How polar cortex contractility controls cell shape is poorly understood. We show a balance between MII paralogs allows a fine-tuning of cortex tension at the polar cortex to maintain cell shape during cytokinesis, with MIIA driving cleavage furrow ingression and bleb formation, and MIIB serving as a stabilizing motor and mediating completion of cytokinesis. As the majority of non-muscle contractile systems are cortical, this tuning mechanism will likely be applicable to numerous processes driven by MII contractility.

cell biology

Sox6: A new modulator of renin expression during physiological conditions

Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells which give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation JG cells undergo expansion. Gene expression profiling comparing resident renal Mesenchymal Stromal Cells (MSCs) with JG cells indicate that the transcription factor Sox6 is highly expressed in JG cells in the adult kidney. In vitro, loss of Sox6 expression reduces differentiation of renal MSCs to renin producing cells. In vivo, Sox6 expression is up-regulated during JG cell expansion. Importantly, knockout of Sox6 in Ren1d+ cells halts the increase in renin expressing cells normally seen during JG cell expansion as well as the typical increase in renin. These results support a previously undefined role for Sox6 in renin expression during normal and pathophysiological conditions.

physiology