Emmy Li

All Publications

• Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tzeng, C. P., Whitwam, T., Boxer, L. D., Li, E., Silberfeld, A., Trowbridge, S., Mei, K., Lin, C., Shamah, R., Griffith, E. C., Renthal, W., Chen, C., Greenberg, M. E. 2023; 120 (44): e2310344120

  Abstract

  Mutations in MECP2 give rise to Rett syndrome (RTT), an X-linked neurodevelopmental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation for its clinical presentation is that loss of MECP2 causes miswiring of neural circuits due to defects in the brain's capacity to respond to changes in neuronal activity and sensory experience. Here, we show that MeCP2 is phosphorylated at four residues in the mouse brain (S86, S274, T308, and S421) in response to neuronal activity, and we generate a quadruple knock-in (QKI) mouse line in which all four activity-dependent sites are mutated to alanines to prevent phosphorylation. QKI mice do not display overt RTT phenotypes or detectable gene expression changes in two brain regions. However, electrophysiological recordings from the retinogeniculate synapse of QKI mice reveal that while synapse elimination is initially normal at P14, it is significantly compromised at P20. Notably, this phenotype is distinct from the synapse refinement defect previously reported for Mecp2 null mice, where synapses initially refine but then regress after the third postnatal week. We thus propose a model in which activity-induced phosphorylation of MeCP2 is critical for the proper timing of retinogeniculate synapse maturation specifically during the early postnatal period.

  View details for DOI 10.1073/pnas.2310344120

  View details for Web of Science ID 001138994000003

  View details for PubMedID 37871205

  View details for PubMedCentralID PMC10623012

• A reference human induced pluripotent stem cell line for large-scale collaborative studies. Cell stem cell Pantazis, C. B., Yang, A., Lara, E., McDonough, J. A., Blauwendraat, C., Peng, L., Oguro, H., Kanaujiya, J., Zou, J., Sebesta, D., Pratt, G., Cross, E., Blockwick, J., Buxton, P., Kinner-Bibeau, L., Medura, C., Tompkins, C., Hughes, S., Santiana, M., Faghri, F., Nalls, M. A., Vitale, D., Ballard, S., Qi, Y. A., Ramos, D. M., Anderson, K. M., Stadler, J., Narayan, P., Papademetriou, J., Reilly, L., Nelson, M. P., Aggarwal, S., Rosen, L. U., Kirwan, P., Pisupati, V., Coon, S. L., Scholz, S. W., Priebe, T., Öttl, M., Dong, J., Meijer, M., Janssen, L. J., Lourenco, V. S., van der Kant, R., Crusius, D., Paquet, D., Raulin, A. C., Bu, G., Held, A., Wainger, B. J., Gabriele, R. M., Casey, J. M., Wray, S., Abu-Bonsrah, D., Parish, C. L., Beccari, M. S., Cleveland, D. W., Li, E., Rose, I. V., Kampmann, M., Calatayud Aristoy, C., Verstreken, P., Heinrich, L., Chen, M. Y., Schüle, B., Dou, D., Holzbaur, E. L., Zanellati, M. C., Basundra, R., Deshmukh, M., Cohen, S., Khanna, R., Raman, M., Nevin, Z. S., Matia, M., Van Lent, J., Timmerman, V., Conklin, B. R., Johnson Chase, K., Zhang, K., Funes, S., Bosco, D. A., Erlebach, L., Welzer, M., Kronenberg-Versteeg, D., Lyu, G., Arenas, E., Coccia, E., Sarrafha, L., Ahfeldt, T., Marioni, J. C., Skarnes, W. C., Cookson, M. R., Ward, M. E., Merkle, F. T. 2022; 29 (12): 1685-1702.e22

  Abstract

  Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

  View details for DOI 10.1016/j.stem.2022.11.004

  View details for PubMedID 36459969