Deciphering Molecular Heterogeneity and Dynamics of Human Hippocampal Neural Stem Cells at Different Ages and Injury States

Overview

Journal Elife

Specialty Biology

Date 2024 Apr 12

PMID 38607670

Authors

Junjun Yao

Shaoxing Dai

Ran Zhu

Ju Tan

Qiancheng Zhao

Yu Yin

Jiansen Sun

Xuewei Du

Longjiao Ge

Jianhua Xu

Chunli Hou

Nan Li

Jun Li

Weizhi Ji

Chuhong Zhu

Runrui Zhang

Tianqing Li

Affiliations

Soon will be listed here.

Abstract

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

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References

Silverman D, Martinez V, Dougherty P, Myers J, Calin G, Amit M . Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk. Cancer Res. 2020; 81(6):1431-1440. PMC: 7969424. DOI: 10.1158/0008-5472.CAN-20-2793. View

Obernier K, Alvarez-Buylla A . Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development. 2019; 146(4). PMC: 6398449. DOI: 10.1242/dev.156059. View

Hao Z, Wei J, Xiao D, Liu R, Xu N, Tang L . Single-cell transcriptomics of adult macaque hippocampus reveals neural precursor cell populations. Nat Neurosci. 2022; 25(6):805-817. DOI: 10.1038/s41593-022-01073-x. View

Butler A, Hoffman P, Smibert P, Papalexi E, Satija R . Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018; 36(5):411-420. PMC: 6700744. DOI: 10.1038/nbt.4096. View

Moreno-Jimenez E, Flor-Garcia M, Terreros-Roncal J, Rabano A, Cafini F, Pallas-Bazarra N . Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease. Nat Med. 2019; 25(4):554-560. DOI: 10.1038/s41591-019-0375-9. View

Ponti G, Obernier K, Guinto C, Jose L, Bonfanti L, Alvarez-Buylla A . Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci U S A. 2013; 110(11):E1045-54. PMC: 3600494. DOI: 10.1073/pnas.1219563110. View

Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck 3rd W . Comprehensive Integration of Single-Cell Data. Cell. 2019; 177(7):1888-1902.e21. PMC: 6687398. DOI: 10.1016/j.cell.2019.05.031. View

Tirosh I, Izar B, Prakadan S, Wadsworth 2nd M, Treacy D, Trombetta J . Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016; 352(6282):189-96. PMC: 4944528. DOI: 10.1126/science.aad0501. View

Zheng G, Terry J, Belgrader P, Ryvkin P, Bent Z, Wilson R . Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017; 8:14049. PMC: 5241818. DOI: 10.1038/ncomms14049. View

10.

Zhang H, Chen H, Liu W, Liu H, Gong J, Wang H . AnimalTFDB: a comprehensive animal transcription factor database. Nucleic Acids Res. 2011; 40(Database issue):D144-9. PMC: 3245155. DOI: 10.1093/nar/gkr965. View

11.

Zhao Y, Chen Y, Miao G, Zhao H, Qu W, Li D . The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. Mol Cell. 2017; 67(6):974-989.e6. DOI: 10.1016/j.molcel.2017.08.005. View

12.

Ayhan F, Kulkarni A, Berto S, Sivaprakasam K, Douglas C, Lega B . Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans. Neuron. 2021; 109(13):2091-2105.e6. PMC: 8273123. DOI: 10.1016/j.neuron.2021.05.003. View

13.

Wu M, Hen R . Functional dissociation of adult-born neurons along the dorsoventral axis of the dentate gyrus. Hippocampus. 2014; 24(7):751-61. PMC: 4222246. DOI: 10.1002/hipo.22265. View

14.

Thines L, Gorisse L, Li Z, Sayedyahossein S, Sacks D . Calmodulin activates the Hippo signaling pathway by promoting LATS1 kinase-mediated inhibitory phosphorylation of the transcriptional coactivator YAP. J Biol Chem. 2022; 298(5):101839. PMC: 9019248. DOI: 10.1016/j.jbc.2022.101839. View

15.

Terreros-Roncal J, Moreno-Jimenez E, Flor-Garcia M, Rodriguez-Moreno C, Trinchero M, Cafini F . Impact of neurodegenerative diseases on human adult hippocampal neurogenesis. Science. 2021; 374(6571):1106-1113. PMC: 7613437. DOI: 10.1126/science.abl5163. View

16.

Daynac M, Pineda J, Chicheportiche A, Gauthier L, Morizur L, Boussin F . TGFβ lengthens the G1 phase of stem cells in aged mouse brain. Stem Cells. 2014; 32(12):3257-65. DOI: 10.1002/stem.1815. View

17.

Mauffrey P, Tchitchek N, Barroca V, Bemelmans A, Firlej V, Allory Y . Progenitors from the central nervous system drive neurogenesis in cancer. Nature. 2019; 569(7758):672-678. DOI: 10.1038/s41586-019-1219-y. View

18.

Liu Q, Wang X, Qin Y, Yan X, Chen H, Huang Q . SPOCD1 promotes the proliferation and metastasis of glioma cells by up-regulating PTX3. Am J Cancer Res. 2018; 8(4):624-635. PMC: 5934553. View

19.

Ugalde C, Lewis V, Stehmann C, McLean C, Lawson V, Collins S . Markers of A1 astrocytes stratify to molecular sub-types in sporadic Creutzfeldt-Jakob disease brain. Brain Commun. 2020; 2(2):fcaa029. PMC: 7425384. DOI: 10.1093/braincomms/fcaa029. View

20.

Macosko E, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M . Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015; 161(5):1202-1214. PMC: 4481139. DOI: 10.1016/j.cell.2015.05.002. View