Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny

被引：2

作者：

Li, Fei ^{[1
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Zhu, Yanling ^{[1
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Wang, Tianyu ^{[1
,2
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,5
,6
,7
]}

Tang, Jun ^{[1
,2
,3
,4
]}

Huang, Yuhua ^{[1
,2
,3
,5
,7
]}

Gu, Jiaming ^{[1
,2
,4
,5
,7
]}

Mai, Yuchan ^{[1
,2
,4
,5
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]}

Wang, Mingquan ^{[1
,2
,4
,5
,6
,7
]}

Zhang, Zhishuai ^{[1
,2
,3
,4
,5
,7
]}

Ning, Jiaying ^{[1
,2
,4
,5
,7
]}

Kang, Baoqiang ^{[1
,2
,4
,5
,7
]}

Wang, Junwei ^{[1
,2
,4
,5
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]}

Zhou, Tiancheng ^{[1
,2
,4
,5
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]}

Cui, Yazhou ^{[8
,9
]}

Pan, Guangjin ^{[1
,2
,3
,4
,5
,6
,7
,8
,9
]}

机构：

[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Joint Sch Life Sci, Key Lab Immune Response & Immunotherapy, Guangzhou 510530, Peoples R China

[2] Guangzhou Med Univ, Guangzhou 510530, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[4] Chinese Acad Sci, Hong Kong Inst Sci & Innovat, Ctr Regenerat Med & Hlth, Hong Kong, Peoples R China

[5] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangdong Hong Kong Joint Lab Stem Cell & Regenera, Guangzhou 510530, Peoples R China

[6] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, GIBH HKU Guangdong Hong Kong Stem Cell & Regenerat, GIBH CUHK Joint Res Lab Stem Cell & Regenerat Med, Guangzhou 510530, Peoples R China

[7] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou 510530, Peoples R China

[8] Shandong First Med Univ & Shandong Acad Med Sci, Biomed Sci Coll, Key Lab Rare & Uncommon Dis Shandong Prov, Jinan 250117, Shandong, Peoples R China

[9] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Med Biotechnol Ctr, Jinan 250117, Shandong, Peoples R China

来源：

CELL REGENERATION | 2024年 / 13卷 / 01期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Hematopoietic stem cell; Transcription factors; Lineage potential; Gene regulatory networks; Human induced pluripotent stem cells; Hematopoietic differentiation; IN-VITRO; FETAL LIVER; CORD BLOOD; T-CELLS; MAINTENANCE; EMBRYO; EMERGE; DIFFERENTIATION; PROLIFERATION; DISTINGUISHES;

D O I：

10.1186/s13619-024-00192-z

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

引用

页数：18

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