Hindbrain boundaries as niches of neural progenitor and stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate

Carmel Hutchings, Yarden Nuriel, Daniel Lazar, Ayelet Kohl, Elizabeth Muir, Olga Genin, Yuval Cinnamon, Hadar Benyamini, Yuval Nevo, Dalit Sela-Donenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The interplay between neural progenitors and stem cells (NPSCs), and their extracellular matrix (ECM) is a crucial regulatory mechanism that determines their behavior. Nonetheless, how the ECM dictates the state of NPSCs remains elusive. The hindbrain is valuable to examine this relationship, as cells in the ventricular surface of hindbrain boundaries (HBs), which arise between any two neighboring rhombomeres, express the NPSC marker Sox2, while being surrounded with the membrane-bound ECM molecule chondroitin sulphate proteoglycan (CSPG), in chick and mouse embryos. CSPG expression was used to isolate HB Sox2+ cells for RNA-sequencing, revealing their distinguished molecular properties as typical NPSCs, which express known and newly identified genes relating to stem cells, cancer, the matrisome and cell cycle. In contrast, the CSPG- non-HB cells, displayed clear neuraldifferentiation transcriptome. To address whether CSPG is significant for hindbrain development, its expression was manipulated in vivo and in vitro. CSPG manipulations shifted the stem versus differentiation state of HB cells, evident by their behavior and altered gene expression. These results provide further understanding of the uniqueness of hindbrain boundaries as repetitive pools of NPSCs in-between the rapidly growing rhombomeres, which rely on their microenvironment to maintain their undifferentiated state during development.

Original languageAmerican English
Pages (from-to)1-20
Number of pages20
JournalDevelopment (Cambridge)
Volume151
Issue number4
DOIs
StatePublished - 2024

Bibliographical note

Publisher Copyright:
© 2024. Published by The Company of Biologists Ltd.

Keywords

  • Chondroitin-sulphate proteoglycan
  • Embryo
  • Extracellular matrix
  • Hindbrain boundaries
  • Neural stem cells
  • Progenitor cells
  • RNA-sequencing

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