preLighters’ choice – A curated selection of recent preprints

preLighters with expertise across developmental and stem cell biology nominate a few recent developmental and stem cell biology (and related) preprints they’re excited about and explain in a few paragraph why. Concise preprint highlights, prepared by the preLighter community – a quick way to spot upcoming trends, new methods and fresh ideas.

Preprint highlights

• Canonical mTOR signaling supports complete fin regeneration selected by Theodora M Stougiannou
• Whole-Cell Proteomics Identifies Novel Regulators of Ciliogenesis Beyond the Axoneme selected by Jawdat Sandakly
• Synthetic lumen rounding directs neural progenitor division mode selected by Sristilekha Nath
• Lamin A/C directs nucleosome-scale chromatin remodeling to define early lineage segregation in mammals selected by Deevitha Balasubramanian
• Abnormal ventricular wall patterning precedes and drives MYBPC3 hypertrophic cardiomyopathy selected by Theodora M Stougiannou

Preprint:

Theodora M Stougiannou

Preprint:

Canonical mTOR signaling supports complete fin regeneration
Josane F. de Sousa, Gabriela Lima, Louise Perez, Michaela Tsanova, Cyrus Bronson, Garrison Boehl, Icyss Sargeant, Rogerio Gomes, Aline C. Dragalzew, Wainna B. Mendes, Igor Schneider

preLight:

Fins, and cells, and signals, and regeneration, oh my! How the Senegal bichir regrows its fins after amputation.

The authors of this preprint investigate fin regeneration in the Senegal bichir (Polypterus senegalus), a type of ray-finned fish capable of full fin regeneration; this biological characteristic is quite impressive on its own, as the fin includes different tissues, such as skeletal, cartilaginous, muscular and connective tissue with complexity comparable to that found in tetrapod limbs.

The preprint authors show that regeneration entails the activation of canonical mTOR cellular programs, as treatment with the mTOR inhibitor rapamycin prevented this regeneration, though wound healing proceeded normally. Signaling was activated upon amputation, first in epithelial cells in the epidermis and then in adjacent mesenchymal cells below the superficial layers, as well as myeloid cell types.

It seems that mTOR programs in myeloid populations are responsible for the coordination of regenerative procedures across different cell types, as well as its eventual resolution.  Moreover, existence of such programs in species of fish highlights the ‘ancient’ evolutionary origins of tissue regeneration, giving hope for application of these principles in other species.

Jawdat Sandakly

Preprint:

Whole-Cell Proteomics Identifies Novel Regulators of Ciliogenesis Beyond the Axoneme
Xiaolu Xu, Yanbao Yu, Tony Zheng, Fiona Clark, Jean Ross, Neha Sindhu, Andre L P Tavares, John B Wallingford, Shuo Wei, Jian Sun

preLight:

Uncovering new players in ciliogenesis by whole-cell proteomics

Motile cilia are microtubule-based organelles that are involved in fundamental biological processes such as embryonic development, signalling, and mucus clearance. Their dysfunction results in several disorders known as ciliopathies.

Several efforts over the years have helped in elucidating the molecular architecture of motile cilia and in understanding ciliary structures and functions. Moreover, previous proteomic studies provided valuable insights into the axonemal composition. However, many molecular regulators of ciliogenesis remain unknown and other critical cellular components beyond the axoneme involved in ciliogenesis require further investigation.

In this preprint, the authors performed a high-resolution whole-cell proteomic profile of multiciliated cells (MCC), whose function is regulated by axonemal proteins, basal bodies, cytoplasmic factors, and nuclear components. They induced MCC cell fate in Xenopus, therefore enriching ciliary proteins and generating mucociliary organoids. Following their high-depth proteomic profiling, they identified several previously uncharacterized proteins that are essential for MCC maintenance and ciliogenesis. Through in situ hybridization, immunostaining, and gene knockdown, they further confirmed the new candidates, thus providing new potential targets to be further explored to gain a better understanding of the mechanisms related to ciliopathies.

Sristilekha Nath

Preprint:

Synthetic lumen rounding directs neural progenitor division mode
Marina Marchenko, Guillermo Martínez Ara, Juslina Pulikkal, Keisuke Ishihara, Miki Ebisuya

preLight:

Cells read lumen geometry to instruct division mode and lineage progression

During early brain development, tissue geometry – including lumen geometry – dynamically changes; a process which varies across species. But does this geometry simply result from development, or does it actively instruct how cells behave?

The authors of this preprint investigate this question by artificially controlling lumen geometry in brain organoids using two approaches: chemical induction of Shroom3, a protein that drives apical constriction and OptoShroom3, an optogenetic system enabling precise, light-controlled activation. The latter enables spatially targeted control without affecting overall Shroom3 levels within the organoids.

The results reveal that lumen geometry is not a passive consequence of development, but an active regulator of cell behavior. Chemically-induced Shroom3 organoids formed much rounder lumens and neural buds, and generated basal progenitor cells faster than controls, while cells gradually switched from vertical to horizontal cleavage planes over time, a critical reorientation since horizontal division results in asymmetric cell division that generates more basal progenitors, whereas vertical division (in controls) maintains more apical progenitors. When the authors used OptoShroom3 to create rounded lumens with localized blue light illumination, apical progenitor cells in target buds similarly shifted toward horizontal cleavage planes within an hour, whereas those without illumination (control bud within the same organoid) did not.

These findings demonstrate that cells ‘read’ their geometric environment to make developmental decisions, suggesting lumen shape as a key determinant, not merely a consequence of morphogenetic outcomes, a principle likely applicable broadly across organs and species. 

Deevitha Balasubramanian

Preprint:

Lamin A/C directs nucleosome-scale chromatin remodeling to define early lineage segregation in mammals
Alice Sherrard, Liangwen Zhong, Caroline Hoppe, Srikar Krishna, Scott Youlten, Curtis W. Boswell, Stephen Cross, Fiona E. Sievers, Goli Ardestani, Denny Sakkas, Liyun Miao, Zachary D. Smith, Berna Sozen, Antonio J. Giraldez

preLight:

Nuclear lamins direct the first lineage decision in mammalian cells

The first lineage decision during mammalian development into the inner cell mass (ICM) and trophectoderm (TE) is well known to be initiated by transcriptional and epigenetic factors and reinforced by mechanical forces. While global chromatin organization is understood to be important for this process, it remains unclear how the fine-scale distribution of chromatin and nucleosomes plays a role in these cell fate decisions.

To investigate this, the authors set up an improved chromatin electron tomography protocol called ChromEMT to observe nanometer-scale sub-nucleosomal structures. Using ChromEMT on human and mouse cell cultures before, during, and after specification into ICM and TE, they identified key differences in chromatin packing density and nucleosome spacing between these lineages. Importantly, they found that TE nuclei have highly compacted chromatin at their nuclear periphery. In line with this increased peripheral compaction, the authors could show that proteins located at the inner nuclear membrane, particularly lamins A and C, are specifically upregulated in TE cells across mammals. Loss of Lamin A/C resulted in loss of peripheral chromatin compaction and upregulation of pluripotency genes in TE cells, suggesting an overall transition to ICM-like characteristics. This, in turn, impairs normal progression through embryogenesis.

In concert with many more supporting findings, this preprint demonstrates how chromatin compaction and nuclear lamins directly shape early mammalian development.

Theodora M Stougiannou

Preprint:

Abnormal ventricular wall patterning precedes and drives MYBPC3 hypertrophic cardiomyopathy
Alejandro Salguero-Jiménez, Alba Pau-Navalón, Marcos Siguero-Álvarez, Carlos Relaño-Rupérez, Javier Santos-Cantador, María Sabater-Molina, Xiaoxi Luo, Laura Lalaguna, Laura Sen-Martín, Daniel Martín Pérez, Abel Galicia Martín, Bin Zhou, Juan Antonio Bernal Rodríguez, Fátima Sánchez-Cabo, Enrique Lara-Pezzi, Jorge Alegre-Cebollada, Juan R. Gimeno-Blanes, Donal MacGrogan, José Luis de la Pompa

preLight:

More ‘heart’, more problems; a natural history of myocardial hypertrophy progression from embryonic development to adulthood and the role of sarcomeric protein mutations (Mybpc3) in its emergence.

The authors of this preprint investigated the developmental biology underlying hypertrophic cardiomyopathy and left ventricular non-compaction in mice. To this end, they used CRISPR-Cas9, a method used to induce genetic alterations, to introduce MYBPC3 frameshift mutations in the mouse genome and then followed these mice from embryonic and fetal development into adulthood. Adult mice with these mutations displayed hypertrophic cardiomyopathy but with no evidence of left ventricular non-compaction, as opposed to humans. These formations began as trabecular enlargement and crypt enlargement during embryonic development and progressed to hypertrophy in adulthood. Lineage tracing studies further showed invasion of cardiomyocytes normally found in compact myocardium (Hey+ cardiomyocytes), into the developing trabeculae, while after birth, Hey+ cardiomyocytes became restricted to compact myocardium and the inner trabecular myocardium underwent hypertrophy. This is associated with downregulation of the Prdm16; this study highlights how the latter has potential to combat myocardial hypertrophy.

This study highlights the natural history of myocardial hypertrophy and how loss of Mybpc3 is associated with reduction in Prdm16 and onset of pathological hypertrophic remodeling.

(No Ratings Yet)
Loading...