Biology subjects

Gluck, C.

Publications and source records attributed to Gluck, C..

2 recordsLinked to original sources

bioRxiv2023

Impaired centrosome biogenesis in kidney stromal progenitors reduces abundance of interstitial lineages and accelerates injury-induced fibrosis

Defective centrosome function can disrupt embryonic kidney development, by causing changes to the renal interstitium that leads to fibrocystic disease pathologies. Yet, it remains unknown how mutations in centrosome genes impact kidney interstitial cells. Here, we examined the consequences of defective centrosome biogenesis on stromal progenitor cell growth, differentiation and fate. Conditional deletion of Cep120, a ciliopathy gene essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of pericytes, interstitial fibroblasts and mesangial cells. This was due to delayed mitosis, increased apoptosis, and changes in Wnt and Hedgehog signaling essential for differentiation of stromal lineages. Cep120 ablation resulted in hypoplastic kidneys with medullary atrophy and delayed nephron maturation. Finally, centrosome loss in the interstitium sensitized kidneys of adult mice, causing rapid fibrosis via enhanced TGF-{beta}/Smad3-Gli2 signaling after renal injury. Our study defines the cellular and developmental defects caused by centrosome dysfunction in embryonic kidney stroma. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/535583v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@a3b059org.highwire.dtl.DTLVardef@8ed18corg.highwire.dtl.DTLVardef@5f573borg.highwire.dtl.DTLVardef@1581c20_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDefective centrosome biogenesis in kidney stroma causes: C_LIO_LIReduced abundance of stromal progenitors, interstitial and mesangial cell populations C_LIO_LIDefects in cell-autonomous and paracrine signaling C_LIO_LIAbnormal/delayed nephrogenesis and tubular dilations C_LIO_LIAccelerates injury-induced fibrosis via defective TGF-{beta}/Smad3-Gli2 signaling axis C_LI

developmental biology↗

bioRxiv2023

Acoustic trapping and navigation of microrobots in the mouse brain vasculature

Many cerebrovascular and neurodegenerative diseases are currently challenging to treat due to the complex and delicate anatomy of the brain. The use of microrobots can create new opportunities in brain research due to their ability to access hard-to-reach regions and empower various biological applications; however, little is known about the functionality of microrobots in the brain, owing to their limited imaging modalities and intravascular challenges such as high blood flow velocities, osmotic pressures, and cellular responses. Here, we present an acoustic, non-invasive, biocompatible microrobot actuation system, for in vivo navigation in the bloodstream, in which microrobots are formed by lipid-shelled microbubbles that aggregate and propel under the force of acoustic irradiation. We investigated their capacities in vitro within a microfluidic 3D setup and in vivo in a living mouse brain. We show that microrobots can self-assemble and navigate upstream in the brain vasculature. Our microrobots achieved upstream velocities of up to 1.5 m/s and overcame blood flows of ~10 mm/s. Our results prove that microbubble-based microrobots are scalable to the complex 3D living milieu. Significance StatementNumerous brain diseases, including ischemic stroke, Alzheimers disease, and glioblastoma, may benefit from local and targeted therapies. Although they show great promise, microrobots have not yet demonstrated successful in vivo navigation inside the brain, as the challenging flow conditions and the complex 3D vascular network in the brain pose fundamental limitations. Here, we apply acoustically driven microrobots with the capacity for self-assembly and real-time navigation, including navigation against blood flow up to 10 mm/s, used for the first time inside the brain vasculature of a living mouse. The ultrasound manipulation of microrobots inside animal models provides a much-needed pathway for the advancement of preclinical research.

bioengineering↗