preLighters’ choice – November’s handpicked 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 single paragraph why. Concise preprint highlights, prepared by the preLighter community – a quick way to spot upcoming trends, new methods and fresh ideas. These preprints can all be found in the November preprint list.

November highlights

• ERK builds a population of short-lived nascent adhesions that produce persistent edge protrusion and cell migration selected by Aline Grata
• A geothermal amoeba sets a new upper temperature limit for eukaryotes selected by Deevitha Balasubramanian
• An ancient transcription factor functions as the master regulator of primary cilia formation selected by Jawdat Sandakly
• Gene editing in “cell villages” enables exploring disease-relevant mutations in many genetic backgrounds
  selected by Manuel Lessi
• Human pluripotent stem cell-derived macrophages modify development of human kidney organoids selected by Theodora M Stougiannou

Preprint:

Aline Grata

ERK builds a population of short-lived nascent adhesions that produce persistent edge protrusion and cell migration
Andrew P. Shepherd, Keith R. Carney, Andrew Elliott, Sangyoon J. Han, Michelle C. Mendoza

preLight:

ERK builds a population of short-lived nascent adhesions that produce persistent edge protrusion and cell migration

How does a cell coordinate the tiny, fast, fragile adhesions at its leading edge to keep moving forward?
In this work, the authors use a clever ERK FRET biosensor targeted specifically to nascent adhesions, letting them pinpoint when and where ERK becomes active as these structures form. They find that ERK activation occurs right within the assembling region via paxillin, and that this local activity promotes both the formation and rapid turnover of nascent adhesions. This work therefore shows that ERK isn’t just about breaking adhesions down, as traditionally emphasized; it fine-tunes a high-turnover adhesion population that keeps protrusions persistent. The rescue experiment, where simply increasing nascent adhesions restores movement even without ERK, demonstrates the functional importance of this fundamental mechanism.
Overall, this study reveals a core principle of how cells balance adhesion dynamics to drive migration, an essential process in development, wound healing, and cancer.

Deevitha Balasubramanian

Preprint:

A geothermal amoeba sets a new upper temperature limit for eukaryotes
H. Beryl Rappaport, Natalie A. Petek-Seoane, Tomáš Tyml, Felix Mikus, Kurt LaButti, Godwin Ani, Jessica K. Niblo, Ethan MacVicar, Rachel M. Shepherd, Ignacio de la Higuera, Samuel J. Lord, Gautam Dey, Gordon V. Wolfe, Omaya Dudin, Shahar Sukenik, Laura A. Katz, Kenneth M. Stedman, Kristen Skruber, Frederik Schulz, R. Dyche Mullins, Angela M. Oliverio

preLight:

Pushing the temperature limit for eukaryotic survival and function

This preprint reports the discovery of a thermophilic amoeba, Incendiamoeba cascadensis, that can survive, grow, and perform metabolic functions at temperatures up to 64°C, setting a new record for the upper temperature limit of eukaryotes. Isolated from a geothermal stream in California, Incendiamoeba represents a new genus in the Tubulinea class of Amoebozoa. The authors perform detailed experiments to characterize its cellular functions, including replication and motility, at high temperatures. They also highlight several features that could help the organism cope with higher and fluctuating temperatures, such as an enrichment of genes involved in calcium signalling, proteostasis, and DNA repair regulation, as well as higher average melting temperature and surface charge of I. cascadensis proteins.

Jawdat Sandakly

Preprint:

An ancient transcription factor functions as the master regulator of primary cilia formation
Weihua Wang, Xiqi Zhang, Yaxuan Qiu, Xiangrui Meng, Sitong Cheng, Yutong Chen, Siqi Liu, Wenhui Chen, Jiayan Yi, Xiwen You, Hongni Liu, Junqiao Xing, Cheng Xu, Haochen Jiang, Haibo Wang, Guangmei Tian, Zhangfeng Hu

preLight:

Old but gold: an ancient transcription factor is repurposed to regulate primary ciliogenesis

Cilia are highly conserved microtubule-based organelles projecting from the cell surface of almost every quiescent or differentiated mammalian cell. They play key roles in signaling and motility, and their dysfunction can lead to a class of genetic disorders known as ciliopathies. There are motile and non-motile (primary cilia) subtypes. While the transcriptional regulators of ciliogenesis in motile cilia are well established, the upstream cell-type-specific transcriptional programs for the primary cilium remain poorly understood.
The authors of this preprint previously identified the conserved transcription factor X chromosome-associated protein 5 (Xap5) as a key regulator for the assembly of motile cilia, which prompted them to investigate its role in primary ciliogenesis. Here, they demonstrate that in somatic cells, Xap5 interacts with the nuclear protein Nono and forms a complex required for primary cilium assembly. This complex activates a downstream transcriptional cascade involving Sox5 and Sox9. Interestingly, they find that loss of Xap5 or Nono impairs primary ciliogenesis. Their findings not only identify Xap5 as a master upstream regulator of primary ciliogenesis, but also provide new insights into the transcriptional machinery behind primary cilium formation.

Manuel Lessi

Preprint:

Gene editing in “cell villages” enables exploring disease-relevant mutations in many genetic backgrounds
Rachel A. Battaglia, Sonia Bolshakova, Ilinca Mazureac, Dhara Liyanage, Noah Pettinari, Autumn Johnson, Ethan Crouse, Sartaj Habib, Isabel Flessas, Ajay Nadig, Derek Hawes, Matthew Tegtmeyer, Caroline Becker, Sulagna Ghosh, Giulio Genovese, Marina Hogan, Adrianna Maglieri, Lindy E. Barrett, Laurence Daheron, Steven A. McCarroll, Ralda Nehme

preLight:

Gene editing in “cell villages” enables exploring disease-relevant mutations in many genetic backgrounds

Gene editing is one of the most widely used tools in biology to study how genetic variation shapes phenotype. Over the past decades, major efforts have focused on using technologies such as CRISPR to introduce mutations in genes of interest and investigate their effects on developmentally relevant features, particularly in stem cells, which provide a flexible and physiologically meaningful model. However, generating mutant cell lines is a labor-intensive process, and the challenge becomes even greater when attempting to assess the same mutation across multiple genetic backgrounds. This is especially important in the context of neurodevelopmental disorders such as schizophrenia, where the same variant can produce distinct phenotypes depending on the genomic background.
How do we overcome these limitations? By growing cells together! In this work, the authors created “cell villages,” in which the inhabitants are stem cells derived from different donors. They performed bulk gene editing across the mixed population, then isolated single clones, validated them, and subsequently deconvolved their donor identity. This strategy enabled the generation of dozens of edited cell lines within a single experiment, improving efficiency while reducing labor, time, and technical variability.
The authors then differentiated the edited lines into neurons and successfully detected donor-specific responses to NRXN1 and LRP1 knockout. This approach substantially increases the throughput of gene editing in human stem cells, expanding both the flexibility of the system and the genetic toolkit available to developmental biologists for studying the effects of single-gene variants across diverse genomic contexts.

Theodora M Stougiannou

Preprint:

Human pluripotent stem cell-derived macrophages modify development of human kidney organoids
Filipa M. Lopes, Ioannis Bantounas, Alexandra Sarov, Adrian S. Woolf, Susan J. Kimber

preLight:

To make a kidney is one thing; to have kidney with immune populations is another. An immune update on the classic organoid recipe.

The authors of this preprint used macrophages derived from human pluripotent stem cells (hPSC) collected at varying maturation stages in vitro, and then added these to organoid cultures of kidney precursors. Three different concentration of macrophages – in comparison to constant numbers of nephrogenic cells – were evaluated, namely concentrations of 1%, 5% and 20%. Addition of early-stage macrophages seemed to increase the percentage area occupied by developing glomeruli, though adding too high a number of macrophages hindered kidney development, evident by the reduction in the overall organoid area and the dysmorphic kidney tissue generated. This study highlights the contribution of elements of the immune system, including macrophages, to the embryonic development of other systems, including physiological development of the kidney.

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