Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling

Abstract Background IL15Rα is highly expressed in brain tissues, especially in hippocampus. IL15Rα knock-out induces the behavior, physiological and molecular changes in mice similar to the phenotype of psychiatric disorders. Results To study how IL15Rα knock-out affects cellular function of the hip...

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Main Authors: Yanting Luo, Yadan Nie, Xuemei Huang, Haixia Wang, Zuoli Sun, Jian Yang, Yi He
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Genomics
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Online Access:https://doi.org/10.1186/s12864-025-11785-6
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author Yanting Luo
Yadan Nie
Xuemei Huang
Haixia Wang
Zuoli Sun
Jian Yang
Yi He
author_facet Yanting Luo
Yadan Nie
Xuemei Huang
Haixia Wang
Zuoli Sun
Jian Yang
Yi He
author_sort Yanting Luo
collection DOAJ
description Abstract Background IL15Rα is highly expressed in brain tissues, especially in hippocampus. IL15Rα knock-out induces the behavior, physiological and molecular changes in mice similar to the phenotype of psychiatric disorders. Results To study how IL15Rα knock-out affects cellular function of the hippocampus in adult mice, we produced 64,399 single-cell transcriptomes from WT and KO mice and identified precursor-like neuron (PLN), a type of neural cells exhibiting precursor-like attributes, as well as four variant glial cell types. PLN displayed top-ranked functional changes despite barely changing in cell counts, along with high abundance of ribosomal genes, heavy energy consumption, quiescent cell-cell communication, intensive distribution in developmental stages, and a widespread yet moderate distribution across adult brain regions. We proposed PLN is in an intermediate and unprepared state, reserved for regulating inhibitory neuron fitness and exerting excitatory-inhibitory balance. We developed “polarization score” to evaluate the degree of cell aggregation and found its relation to transcription redundancy. Conclusions In summary, we demonstrate the precursor-like attributes of PLN and its potential as a regulatory fulcrum for adjusting brain’s excitatory-inhibitory balance and robustness in IL15Rα-KO mice.
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spelling doaj-art-3558dd8b644a4b2198df143ee3ac85bc2025-08-20T03:03:41ZengBMCBMC Genomics1471-21642025-07-0126111710.1186/s12864-025-11785-6Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodelingYanting Luo0Yadan Nie1Xuemei Huang2Haixia Wang3Zuoli Sun4Jian Yang5Yi He6Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityAbstract Background IL15Rα is highly expressed in brain tissues, especially in hippocampus. IL15Rα knock-out induces the behavior, physiological and molecular changes in mice similar to the phenotype of psychiatric disorders. Results To study how IL15Rα knock-out affects cellular function of the hippocampus in adult mice, we produced 64,399 single-cell transcriptomes from WT and KO mice and identified precursor-like neuron (PLN), a type of neural cells exhibiting precursor-like attributes, as well as four variant glial cell types. PLN displayed top-ranked functional changes despite barely changing in cell counts, along with high abundance of ribosomal genes, heavy energy consumption, quiescent cell-cell communication, intensive distribution in developmental stages, and a widespread yet moderate distribution across adult brain regions. We proposed PLN is in an intermediate and unprepared state, reserved for regulating inhibitory neuron fitness and exerting excitatory-inhibitory balance. We developed “polarization score” to evaluate the degree of cell aggregation and found its relation to transcription redundancy. Conclusions In summary, we demonstrate the precursor-like attributes of PLN and its potential as a regulatory fulcrum for adjusting brain’s excitatory-inhibitory balance and robustness in IL15Rα-KO mice.https://doi.org/10.1186/s12864-025-11785-6IL15RαHippocampusSingle cell transcriptomePrecursor-like neural cell
spellingShingle Yanting Luo
Yadan Nie
Xuemei Huang
Haixia Wang
Zuoli Sun
Jian Yang
Yi He
Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling
BMC Genomics
IL15Rα
Hippocampus
Single cell transcriptome
Precursor-like neural cell
title Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling
title_full Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling
title_fullStr Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling
title_full_unstemmed Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling
title_short Single-cell transcriptome of mouse hippocampus identifies neural precursor-like cells, and reveals IL15Rα knock out-mediated neuron remodeling
title_sort single cell transcriptome of mouse hippocampus identifies neural precursor like cells and reveals il15rα knock out mediated neuron remodeling
topic IL15Rα
Hippocampus
Single cell transcriptome
Precursor-like neural cell
url https://doi.org/10.1186/s12864-025-11785-6
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