Mapping the two distinct proliferative bursts early in T-cell development

IF 3.2 4区 医学 Q3 CELL BIOLOGY
Seungyoul Oh, Dhruti Parikh, Jiyao Xiao, Xin Liu, Karen Gu, Mark MW Chong
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引用次数: 0

Abstract

T-cell development occurs in the thymus and is tightly regulated to produce a diverse enough repertoire of mature T cells that can recognize any potential pathogen. The development of T cells is dependent on small numbers of uncommitted precursors that continually seed the thymus from the bone marrow. As they progress along the developmental pathway, there is a massive expansion in cell number to generate the necessary diversity in T-cell receptor chain usage. It is recognized that there are two proliferative bursts that occur early in T-cell development, one prior to β-selection and one after, and these are responsible for the expansion. While the proliferation following β-selection is well-characterized, the earlier proliferative burst has yet to be precisely defined. In this study, we employ single-cell RNA sequencing coupled to trajectory inference methods to pinpoint when in T-cell development thymocytes are induced into cell cycle. We show that the first proliferative burst is initiated in the double-negative (DN) 2a stage before T lineage commitment occurs, with cell cycling downregulated by the DN3a stage. A second burst is then initiated at the DN3b stage, immediately after β-selection. We subsequently employ fluorescence-activated cell sorting–based analysis for DNA content to confirm these two proliferative bursts.

Abstract Image

绘制t细胞发育早期的两种不同的增殖爆发
T细胞的发育发生在胸腺中,并受到严格的调控,以产生足够多样化的成熟T细胞,这些成熟T细胞可以识别任何潜在的病原体。T细胞的发育依赖于少量未确定的前体,这些前体不断地从骨髓中植入胸腺。随着它们在发育途径上的进展,细胞数量大量增加,以产生t细胞受体链使用的必要多样性。人们认识到,在t细胞发育早期有两次增殖爆发,一次发生在β选择之前,一次发生在β选择之后,它们负责扩增。虽然β选择后的增殖已被很好地描述,但早期的增殖爆发尚未被精确定义。在这项研究中,我们采用单细胞RNA测序结合轨迹推断方法来确定t细胞发育过程中胸腺细胞何时被诱导进入细胞周期。我们发现,在T谱系发生之前,第一次增殖爆发是在双阴性(DN) 2a阶段开始的,细胞周期在DN3a阶段下调。在β选择后,DN3b阶段立即开始第二次爆发。我们随后采用荧光激活细胞分选为基础的DNA含量分析,以确认这两个增殖爆发。
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来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
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