Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution

被引：36

作者：

Cao, Jing ^{[1
,2
,3
,4
]}

Yao, Qi Jason ^{[5
]}

Wu, Jiao ^{[1
,2
,3
,4
]}

Chen, Xiaonan ^{[7
]}

Huang, Lin ^{[1
,2
,3
,4
]}

Liu, Wanshan ^{[1
,2
,3
,4
]}

Qian, Kun ^{[1
,2
,3
,4
]}

Wan, Jing-Jing ^{[7
]}

Zhou, Bo O. ^{[5
,6
]}

机构：

[1] Shanghai Jiao Tong Univ, Inst Med Robot, Sch Biomed Engn, State Key Lab Syst Med Canc, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Acad Expt Med, Shanghai 200030, Peoples R China

[3] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Key Lab Gynecol Oncol,Dept Obstet & Gyne, Shanghai 200127, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Div Cardiol, Renji Hosp, Shanghai 200127, Peoples R China

[5] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci,State Key Lab Cell Bi, Shanghai 200031, Peoples R China

[6] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, State Key Lab Expt Hematol, Haihe Lab Cell Ecosyst, Tianjin 300020, Peoples R China

[7] East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China

来源：

CELL METABOLISM | 2024年 / 36卷 / 01期

关键词：

MASS-SPECTROMETRY; LYMPHOID PROGENITORS; IDENTIFICATION; YEAST;

D O I：

10.1016/j.cmet.2023.12.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Metabolic status is crucial for stem cell functions; however, the metabolic heterogeneity of endogenous stem cells has never been directly assessed. Here, we develop a platform for high -throughput single -cell metabolomics (hi-scMet) of hematopoietic stem cells (HSCs). By combining flow cytometric isolation and nanoparticleenhanced laser desorption/ionization mass spectrometry, we routinely detected >100 features from single cells. We mapped the single -cell metabolomes of all hematopoietic cell populations and HSC subpopulations with different division times, detecting 33 features whose levels exhibited trending changes during HSC proliferation. We found progressive activation of the oxidative pentose phosphate pathway (OxiPPP) from dormant to active HSCs. Genetic or pharmacological interference with OxiPPP increased reactive oxygen species level in HSCs, reducing HSC self -renewal upon oxidative stress. Together, our work uncovers the metabolic dynamics during HSC proliferation, reveals a role of OxiPPP for HSC activation, and illustrates the utility of hi-scMet in dissecting metabolic heterogeneity of immunophenotypically defined cell populations.

引用

页码：209 / 221.e6

页数：20

共 45 条

[11] Analysis of single algal cells by combining mass spectrometry with Raman and fluorescence mapping [J].