Biology subjects

Pfeiffer, S.

Publications and source records attributed to Pfeiffer, S..

4 recordsLinked to original sources

bioRxiv2025

Oocyte surface proteins EGG-1 and EGG-2 are required for eggshell integrity in Caenorhabditis elegans

Metazoan eggs are surrounded by a specialized coat of extracellular matrix that mediates sperm-egg interactions. This coat is rapidly remodeled after fertilization to form a barrier that prevents polyspermy, protects against environmental insults, and provides structural support to the developing embryo. In C. elegans several oocyte surface proteins have been identified that mediate these events. However, whether two of these proteins, EGG-1 and EGG-2, are required for fertilization or downstream events has been unclear. Here, we address this question using more recent advances in genome editing tools through the creation of egg-1 egg-2 deletions of the endogenous loci. We found that egg-1 egg-2 oocytes are fertilization competent and form rudimentary eggshells. While the integrity of the egg-1 egg-2 eggshells are compromised and often rupture within the uterus, surprisingly, some embryos are capable of undergoing several rounds of cell division. Overall, our findings demonstrate that EGG-1 and EGG-2 are not required for fertilization but are involved in post-fertilization processes.

developmental biology↗

bioRxiv2024

Hematological phenotypes in GATA2 deficiency syndrome arise from secondary injuries and maladaptation to proliferation

The GATA2 transcription factor is a pivotal regulator of hematopoiesis. Disruptions in the GATA2 gene drive severe hematologic abnormalities and are associated with an increased risk of myelodysplastic syndromes and acute myeloid leukemia; however, the mechanisms underlying the pathophysiology of GATA2 deficiency remain still unclear. We developed two different mouse models that are based on serial and limiting donor cell transplantation of (aged) GATA2 haploinsufficient cells and mirror the symptoms of GATA2 deficiency. Similar to what has been observed in patients, our models show that GATA2 haploinsufficiency leads to B lymphopenia, monocytopenia, lethal bone marrow failure (BMF), myelodysplasia and leukemia. Leukemia arises exclusively as a result of BMF, driven by somatic aberrations and accompanied by increased Myc target expression and genomic instability. These findings were confirmed in human GATA2+/- K562 cell lines showing defects in cytokinesis and are in line with the fact that monosomy 7 and trisomy 8 are frequent events in patients with MDS. Key pointsO_LIIn a mouse model for GATA2 deficiency, leukemia emerges from bone marrow failure C_LIO_LIMaladaptation to proliferative signals and chromosomal segregation defects contribute to the hematological phenotypes in GATA2 deficiency C_LI

cell biology↗

bioRxiv2024

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels

HighlightsO_LIAlveolar organoids are formed with a two-step, Matrigel-free method in a semi-synthetic hyaluronic acid (HA) hydrogel C_LIO_LIThe two-step method offers control over alveolar size, density, and growth C_LIO_LIAlveolar organoids maintain their AT2 identity in HA hydrogels C_LIO_LIAlveolar organoids secrete nascent extracellular matrix supporting organoid growth without Matrigel C_LI SummaryHuman induced pluripotent stem cell (iPSC) derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse-sarcoma derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in the synthetic hydrogels. Thus, the synthetic gels described here allow us to de-couple exogenous and nascent ECM in order to interrogate the role of ECM in organoid formation.

cell biology↗

bioRxiv2020

The effects of seasonal climate variability on dengueannual incidence in Hong Kong: A modellingstudy

In recent years, dengue has been rapidly spreading and growing in the tropics and subtropics. Located in southern China, Hong Kongs subtropical monsoon climate may favour dengue vector populations and increase the chance of disease transmissions during the rainy summer season. An increase in local dengue incidence has been observed in Hong Kong ever since the first case in 2002, with an outbreak reaching historically high case numbers in 2018. However, the effects of seasonal climate variability on recent outbreaks are unknown. As the local cases were found to be spatially clustered, we developed a Poisson generalized linear mixed model using pre-summer monthly total rainfall and mean temperature to predict annual dengue incidence (the majority of local cases occur during or after the summer months), over the period 2002-2018 in three pre-defined areas of Hong Kong. Using leave-one-out cross-validation, 5 out of 6 observations of area-specific outbreaks during the major outbreak years 2002 and 2018 were able to be predicted. 42 out of a total of 51 observations (82.4%) were within the 95% confidence interval of the annual incidence predicted by our model. Our study found that the rainfall before and during the East Asian monsoon (pre-summer) rainy season is negatively correlated with the annual incidence in Hong Kong while the temperature is positively correlated. Hence, as mosquito control measures in Hong Kong are intensified mainly when heavy rainfalls occur during or close to summer, our study suggests that a lower-than-average intensity of pre-summer rainfall should also be taken into account as an indicator of increased dengue risk.

ecology↗