Biology subjects

Nourreddine, S.

Publications and source records attributed to Nourreddine, S..

3 recordsLinked to original sources

bioRxiv2024

A PERTURBATION CELL ATLAS OF HUMAN INDUCED PLURIPOTENT STEM CELLS

Towards comprehensively investigating the genotype-phenotype relationships governing the human pluripotent stem cell state, we generated an expressed genome-scale CRISPRi Perturbation Cell Atlas in KOLF2.1J human induced pluripotent stem cells (hiPSCs) mapping transcriptional and fitness phenotypes associated with 11,739 targeted genes. Using the transcriptional phenotypes, we created a minimum distortion embedding map of the pluripotent state, demonstrating rich recapitulation of protein complexes, such as strong co-clustering of MRPL, BAF, SAGA, and Ragulator family members. Additionally, we uncovered transcriptional regulators that are uncoupled from cell fitness, discovering potential novel pluripotency (JOSD1, RNF7) and metabolic factors (ZBTB41). We validated these findings via phenotypic, protein-interaction, and metabolic tracing assays. Finally, we propose a contrastive human-cell engineering framework (CHEF), a machine learning architecture that learns from perturbation cell atlases to predict perturbation recipes that achieve desired transcriptional states. Taken together, our study presents a comprehensive resource for interrogating the regulatory networks governing pluripotency.

bioengineering↗

bioRxiv2024

Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines

This article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools, status, and future directions. CM4AI is the Functional Genomics Data Generation Project in the U.S. National Institute of Healths (NIH) Bridge2AI program. Its overarching mission is to produce ethical, AI-ready datasets of cell architecture, inferred from multimodal data collected for human cell lines, to enable transformative biomedical AI research.

systems biology↗

bioRxiv2022

Proteomic analysis of the actin cortex in interphase and mitosis

In animal cells, many shape changes are driven by gradients in the contractile tension of the actomyosin cortex, a thin cytoskeletal network that supports the plasma membrane. Elucidating how cortical tension is controlled is thus essential for understanding cell and tissue morphogenesis. Increasing evidence shows that alongside myosin II activity, actin network organisation and composition are key to cortex tension regulation. However, how cortex composition changes when cortical tension changes remains poorly understood. Here, we compared cortices from cells in interphase and in mitosis, as mitosis entry is associated with a strong increase in cortical tension. We purified cortex-enriched cellular fractions and analysed their composition using mass spectrometry, identifying 922 proteins consistently represented in both interphase and mitotic cortices. We curated this dataset by focusing on actin-related proteins, narrowing down to 238 candidate regulators of the cortex during the mitotic cortical tension increase. Among these candidates, our analysis pointed to a role for septins, and in particular septin 9, in the control of mitotic cell rounding. Overall, our study brings insight into the regulation of mitotic rounding, and paves the way for systematic investigations of the regulation of cell surface mechanics.

cell biology↗