Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesis

doi:10.1101/2024.11.22.624575

	Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesis
	You, Chenyu1 ; Zhang, Zhen 1; Li, Lin1 ; Sun, Jianlong 1,2
	2024-11-22
状态	已发表
摘要	Hematopoietic stem cells (HSC) maintain lifelong hematopoiesis. However, in current clonal analyses with unbiased "barcoding" approaches, steady-state hematopoietic clones in young and middle-aged adults rarely have detectable HSCs, which precludes comprehensive interrogation of HSC clonal behaviors. In the current study, we used the previously described Sleeping Beauty transposon model to investigate HSC self-renewal and differentiation at a clonal level following a lifelong chase that significantly enriched HSC-derived clones. From seventeen mice, we detected over seventy thousand clones in native hematopoiesis that reflected the known HSC differentiation biases observed in transplantation. Our data indicated an intimate connection between megakaryocytic-restricted differentiation and HSC self-renewal expansion. By comparing the differentiation patterns of clones derived from transplanted HSCs, we further demonstrated the abilities of HSCs to preserve their cell fates towards self-renewal or multilineage differentiation. Unlike HSCs, clonal expansion in multipotent progenitors was associated with either a differentiation-active or differentiation-indolent state. Moreover, the clonal expansion events in the more differentiated stem and progenitor cells, but not the most primitive HSCs, drove clonal expansion in the megakaryocyte and myeloid cell lineages. Our study provided a comprehensive portrait of native hematopoiesis at a clonal level and revealed the general patterns in which HSCs maintained self-renewal and multi-lineage differentiation.
语种	英语
DOI	10.1101/2024.11.22.624575
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:119312200
WOS类目	Developmental Biology
资助项目	National Natural Science Foundation of China[81970102] ; National Key R&D Program of China["2020YFA0710800","2021YFA0804700"]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/467836
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_李林组生命科学与技术学院_博士生
通讯作者	Li, Lin; Sun, Jianlong
作者单位	1.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Shanghai Tech Univ, State Key Lab Adv Med Mat & Devices, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	You, Chenyu,Zhang, Zhen,Li, Lin,et al. Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesis. 2024.