A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis

Daniel A. Berg, Yijing Su, Dennisse Jimenez-Cyrus, Aneek Patel, Nancy Huang, David Morizet, Stephanie Lee, Reeti Shah, Francisca Rojas Ringeling, Rajan Jain, Jonathan A. Epstein, Qing Feng Wu, Stefan Canzar, Guo Li Ming*, Hongjun Song, Allison M. Bond

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)


New neurons arise from quiescent adult neural progenitors throughout life in specific regions of the mammalian brain. Little is known about the embryonic origin and establishment of adult neural progenitors. Here, we show that Hopx+ precursors in the mouse dentate neuroepithelium at embryonic day 11.5 give rise to proliferative Hopx+ neural progenitors in the primitive dentate region, and they, in turn, generate granule neurons, but not other neurons, throughout development and then transition into Hopx+ quiescent radial glial-like neural progenitors during an early postnatal period. RNA-seq and ATAC-seq analyses of Hopx+ embryonic, early postnatal, and adult dentate neural progenitors further reveal common molecular and epigenetic signatures and developmental dynamics. Together, our findings support a “continuous” model wherein a common neural progenitor population exclusively contributes to dentate neurogenesis throughout development and adulthood. Adult dentate neurogenesis may therefore represent a lifelong extension of development that maintains heightened plasticity in the mammalian hippocampus.

Original languageEnglish
Pages (from-to)654-668.e15
Number of pages31
Issue number3
Early online date28 Mar 2019
Publication statusPublished - 18 Apr 2019

Bibliographical note

Data and Software Availability: The access number for the RNA-seq and ATAC-seq data reported in this study is NCBI GEO: GSE125315.

Acknowledgments: We thank K.M. Christian for comments, members of Ming and Song laboratories for discussion, D. Johnson and B. Temsamrit for technical support, J. Schnoll for lab coordination, and V. Yoon and Y. Huang for providing Apoe-GFP transgenic mouse tissue.
This work was supported by grants from the NIH (P01NS097206 and R37NS047344 to H.S., R35NS097370 and R01MH105128 to G.-L.M., R35HL140018 to J.A.E., and DP2HL147123 to R.J.) and by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to G.-L.M.). R.J. was supported by the Burroughs Wellcome Foundation. D.A.B. was supported by an EMBO postdoctoral fellowship and a grant from the Swedish Research Council.

Author Contributions: D.A.B and A.M.B co-led the project and contributed equally to this work. Y.S., D.J.-C., R.S., A.P., N.H., D.M., S.L., F.R.R., Q.-F.W., and S.C. contributed to additional data collection and analyses. R.J. and J.A.E. contributed reagents. D.A.B., A.M.B., G.-L.M., and H.S. wrote the paper.


  • brain development
  • chromatin landscape profiling
  • dentate gyrus
  • gene expression profiling
  • hippocampus
  • Hopx
  • lineage tracing
  • neural stem cells
  • neurogenesis


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