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Jing, Junjun; Feng, Jifan; Yuan, Yuan; Guo, Tingwei; Lei, Jie; Pei, Fei; Ho, Thach-Vu; Chai, Yang. Nature Communications. vol. 13(1), 4803. August 2022.
Cranial neural crest cells are an evolutionary innovation of vertebrates for craniofacial development and function, yet the mechanisms that govern the cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Using the mouse molar as a model, we perform single-cell transcriptome profiling to interrogate the cell fate diversification of postmigratory cranial neural crest cells. We reveal the landscape of transcriptional heterogeneity and define the specific cellular domains during the progression of cranial neural crest cell-derived dental lineage diversification, and find that each domain makes a specific contribution to distinct molar mesenchymal tissues. Furthermore, IGF signaling-mediated cell-cell interaction between the cellular domains highlights the pivotal role of autonomous regulation of the dental mesenchyme. Importantly, we reveal cell-type-specific gene regulatory networks in the dental mesenchyme and show that Foxp4 is indispensable for the differentiation of periodontal ligament. Our single-cell atlas provides comprehensive mechanistic insight into the cell fate diversification process of the cranial neural crest cell-derived odontogenic populations.
Awotoye, Waheed; Mossey, Peter A.; Hetmanski, Jacqueline B.; Gowans, Lord J. J.; Eshete, Mekonen A.; Adeyemo, Wasiu L.; Alade, Azeez; Zeng, Erliang; Adamson, Olawale; Naicker, Thirona; Anand, Deepti; Adeleke, Chinyere; Busch, Tamara; Li, Mary; Petrin, Aline; Aregbesola, Babatunde S.; Braimah, Ramat O.; Oginni, Fadekemi O.; Oladele, Ayodeji O.; Oladayo, Abimbola; Kayali, Sami; Olotu, Joy; Hassan, Mohaned; Pape, John; Donkor, Peter; Arthur, Fareed K. N.; Obiri-Yeboah, Solomon; Sabbah, Daniel K.; Agbenorku, Pius; Plange-Rhule, Gyikua; Oti, Alexander Acheampong; Gogal, Rose A.; Beaty, Terri H.; Taub, Margaret; Marazita, Mary L.; Schnieders, Michael J.; Lachke, Salil A.; Adeyemo, Adebowale A.; Murray, Jeffrey C.; Butali, Azeez. Scientific Reports. vol. 12(1), 11743. July 2022.
The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.
Schuler, R.E.; Bugacov, A.; Hacia, J.G.; Ho, T.V.; Iwata, J.; Pearlman, L.; Samuels, B.D.; Williams, C.; Zhao, Z.; Kesselman, C.; Chai, Y.. Journal of Dental Research. , 002203452211079. July 2022.
The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research of the National Institutes of Health, was established in 2009 with the recognition that dental and craniofacial research are increasingly data-intensive disciplines. Data sharing is critical for the validation and reproducibility of results as well as to enable reuse of data. In service of these goals, data ought to be FAIR: Findable, Accessible, Interoperable, and Reusable. The FaceBase data repository and educational resources exemplify the FAIR principles and support a broad user community including researchers in craniofacial development, molecular genetics, and genomics. FaceBase demonstrates that a model in which researchers “self-curate” their data can be successful and scalable. We present the results of the first 2.5 y of FaceBase’s operations as an open community and summarize the data sets published during this period. We then describe a research highlight from work on the identification of regulatory networks and noncoding RNAs involved in cleft lip with/without cleft palate that both used and in turn contributed new findings to publicly available FaceBase resources. Collectively, FaceBase serves as a dynamic and continuously evolving resource to facilitate data-intensive research, enhance data reproducibility, and perform deep phenotyping across multiple species in dental and craniofacial research.