التفاصيل البيبلوغرافية
العنوان: |
Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus. |
المؤلفون: |
Rasetto NB, Giacomini D, Berardino AA, Waichman TV, Beckel MS, Di Bella DJ, Brown J, Davies-Sala MG, Gerhardinger C, Lie DC, Arlotta P, Chernomoretz A, Schinder AF |
المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 11. Date of Electronic Publication: 2024 Jan 11. |
نوع المنشور: |
Preprint |
اللغة: |
English |
بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
مستخلص: |
The adult hippocampus generates new granule cells (aGCs) that exhibit distinct functional capabilities along development, conveying a unique form of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like neural stem cells (RGL) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to follow newborn aGCs along differentiation using single-nuclei RNA sequencing (snRNA-seq). Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple sequential immature stages bearing increasing levels of effector genes supporting growth, excitability and synaptogenesis. Remarkably, four discrete cellular states were defined by the expression of distinct sets of transcription factors (TFs): quiescent neural stem cells, proliferative progenitors, postmitotic immature aGCs, and mature aGCs. The transition from immature to mature aCGs involved a transcriptional switch that shutdown molecular cascades promoting cell growth, such as the SoxC family of TFs, to activate programs controlling neuronal homeostasis. Indeed, aGCs overexpressing Sox4 or Sox11 remained stalled at the immature state. Our results unveil precise molecular mechanisms driving adult neural stem cells through the pathway of neuronal differentiation. |
التعليقات: |
Update in: Sci Adv. 2024 Jul 19;10(29):eadp6039. doi: 10.1126/sciadv.adp6039. (PMID: 39028813) |
معلومات مُعتمدة: |
R01 NS103758 United States NS NINDS NIH HHS; R01 NS128117 United States NS NINDS NIH HHS |
تواريخ الأحداث: |
Date Created: 20240123 Latest Revision: 20240802 |
رمز التحديث: |
20240802 |
مُعرف محوري في PubMed: |
PMC10802403 |
DOI: |
10.1101/2023.11.03.565477 |
PMID: |
38260428 |
قاعدة البيانات: |
MEDLINE |