David Chen
The Wnt signaling pathway, an important pathway in the neural development process, affects the differentiation of mouse embryonic stem cells (mESCs) to mature neural cells. CRISPR-Cas9 was used in mESCs to knock out Notum and/or Sfrp1, key genes in Wnt signaling. Immunofluorescence and single cell RNA sequencing (scRNAseq) were then used to study neural cells at various stages of development. As part of the Human Cell Atlas project, an understanding of immune cells at the single cell level is desirable. scRNAseq libraries were prepared from immune cells harvested from several different organ sites and from many different donors. The data was then used to study the differences in the transcriptomes across different immune sites and across an age spectrum. There is currently a paucity of information in regard to understanding exactly how the immune system responds to vaccines, particularly what happens as an early response. Immune cells from various organ sites were stimulated with different vaccines such as Pfizer's COVID-19 vaccine or the Measles-Mumps-Rubella vaccine. scRNAseq libraries from stimulated and unstimulated cells were prepared to study how vaccines affect immune cell composition and gene expression.
Domínguez Conde C, Xu C, Jarvis LB, Rainbow DB, Wells SB, Gomes T, Howlett SK, Suchanek O, Polanski K, King HW, Mamanova L, Huang N, Szabo PA, Richardson L, Bolt L, Fasouli ES, Mahbubani KT, Prete M, Tuck L, Richoz N, Tuong ZK, Campos L, Mousa HS, Needham EJ, Pritchard S, Li T, Elmentaite R, Park J, Rahmani E, Chen D, Menon DK, Bayraktar OA, James LK, Meyer KB, Yosef N, Clatworthy MR, Sims PA, Farber DL, Saeb-Parsy K, Jones JL, Teichmann SA. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science. 2022 May 13;376(6594):eabl5197.
Poon MML, Caron DP, Wang Z, Wells SB, Chen D, Meng W, Szabo PA, Lam N, Kubota M, Matsumoto R, Rahman A, Luning Prak ET, Shen Y, Sims PA, Farber DL. Tissue adaptation and clonal segregation of human memory T cells in barrier sites. Nat Immunol. 2023 Feb;24(2):309-319.
Matsumoto R, Gray J, Rybkina K, Oppenheimer H, Levy L, Friedman LM, Khamaisi M, Meng W, Rosenfeld AM, Guyer RS, Bradley MC, Chen D, Atkinson MA, Brusko TM, Brusko M, Connors TJ, Luning Prak ET, Hershberg U, Sims PA, Hertz T, Farber DL. Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity. Nat Immunol. 2023 Aug;24(8):1370-1381.
Wells SB, Rainbow DB, Mark M, Szabo PA, Ergen C, Maceiras AR, Caron DP, Rahmani E, Benuck E, Amiri VVP, Chen D, Wagner A, Howlett SK, Jarvis LB, Ellis KL, Kubota M, Matsumoto R, Mahbubani K, Saeb-Parsy K, Dominguez-Conde C, Richardson L, Xu C, Li S, Mamanova L, Bolt L, Wilk A, Teichmann SA, Farber DL, Sims PA, Jones JL, Yosef N. Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age. bioRxiv [Preprint]. 2024 Jan 4:2024.01.03.573877.
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