Biology subjects

Herrera, J. A. R.

Publications and source records attributed to Herrera, J. A. R..

3 recordsLinked to original sources

bioRxiv2023

Real time quantification of apical polarity protein reveals novel dynamic processes in luminal network establishment and remodeling in the pancreas

During embryogenesis dynamic changes in tissue architecture transform primitive anlages to functional organs. Here we document in real time how pancreatic lumens are derived and transformed using a new apical-polarity mouse reporter. Our 4D imaging data reveals dynamic remodeling of apical proteins and lumens to primarily drive each stage of pancreatic duct development. Furthermore, we pinpoint two unique transitions during lumenogenesis. Contrary to current "de novo" models of polarity acquisition, we show that expansion and rearrangement of the pre-existing central primary lumen drives early network growth. We also document how the endocrine promoting niche - a "plexus" of interconnected ducts - is resolved. We show that an arborized network forms by gradual closing of ductal loops, rather than via pruning. These novel tissue dynamics provide a new framework within which cell and molecular signaling can be investigated to better understand the interplay between organ architecture and cell fate.

developmental biology↗

bioRxiv2023

nf-core/marsseq: systematic pre-processing pipeline for MARS-seq experiments

MotivationAs a result of advancing single sequencing technology (scRNA-seq), it has become possible to study gene regulatory mechanism(s) and their influence on evolving cell states in time at the level of individual cells. Since 2009, numerous scRNA-seq protocols have been developed, each with its own advantages, disadvantages and library preparation complexities (Ziegenhain et al. 2017). However, the interpretation of data arising from these techniques often shares similar limitations, such as the lack of a standardized pre-processing workflow and consistent data reproducibility. Here we focus on the standardization of the plate based Massively Parallel RNA Single cell Sequencing (MARS-seq, Jaitin et al. 2014) pre-processing pipeline as described in MARS-seq2.0 (Keren-Shaul et al. 2019), which was developed at the Weizmann Institute of Science. ResultsTo overcome the limitations mentioned above, we have taken the original MARS-seq2.0 pipeline and revised it to enable implementation using the nf-core framework (Ewels et al. 2020). By doing so, we have simplified pipeline execution enabling streamlined application, with increased transparency and scalability. Additionally, we have further improved the pipeline by implementing a custom workflow for RNA velocity estimation. Availability and implementationThe pipeline is part of the nf-core bioinformatics community and is freely available at https://github.com/nf-core/marsseq with data analysis at https://github.com/brickmanlab/proks-et-al-2023.

bioinformatics↗

bioRxiv2022

Expansion of Ventral Foregut Primes the Enhancer Landscape for Organ Specific Differentiation

Cell proliferation is fundamental for almost all stages of development and differentiation that require an increase cell number. Although cell cycle phase has been associated with differentiation, the actual process of proliferation is not seen as having a specific role. Here we exploit human embryonic stem cell derived endodermal progenitors that we find are an in vitro model for the ventral foregut. These cells exhibit expansion dependent increases in differentiation efficiency to pancreatic progenitors that are linked to organ-specific enhancer priming at the level of chromatin accessibility and the decommissioning of lineage inappropriate enhancers. Our findings suggest that cell proliferation in embryonic development is about more than tissue expansion, it is required to ensure equilibration of gene regulatory networks allowing cells to become primed for future differentiation. The use of expansion of lineage specific intermediates may therefore be an important step in high fidelity in vitro differentiation.

developmental biology↗