Krankel, A. | bioRxiv Science

bioRxiv2024

Canonical and non-canonical PRC1 differentially contribute to the regulation of neural stem cell fate

Neocortex development is characterized by sequential phases of neural progenitor cell (NPC) expansion, neurogenesis and gliogenesis. Polycomb-mediated epigenetic mechanisms are known to play important roles in regulating the lineage potential of NPCs during development. The composition of Polycomb Repressive Complex 1 (PRC1) is highly diverse in mammals and was hypothesized to contribute to context-specific regulation of cell fate. Here, we have performed side-by-side comparison of the role of canonical PRC1.2/1.4 and non-canonical PRC1.3/1.5, all of which are expressed in the developing neocortex, in NSC proliferation and differentiation. We found that the deletion of Pcgf2/4 in NSCs led to a strong reduction in proliferation and to altered lineage fate, both during the neurogenic and gliogenic phase, whereas Pcgf3/5 played a minor role. Mechanistically, genes encoding stem cell and neurogenic factors were bound by PRC1 and differentially expressed upon Pcgf2/4 deletion. Thus, rather than different PRC1 sub-complexes contributing to different phases of neural development, we found that canonical PRC1 played a more significant role in NSC regulation during proliferative, neurogenic and gliogenic phases compared to non-canonical PRC1.

developmental biology↗

bioRxiv2021

A single-cell atlas of de novo β-cell regeneration reveals the contribution of hybrid β/δ cells to diabetes recovery in zebrafish

Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we use single-cell transcriptomics to map de novo {beta}-cell regeneration during induction and recovery from diabetes in zebrafish. We show that the zebrafish has evolved two distinct types of somatostatin-producing {delta}-cells, which we term {delta}1- and {delta}2-cells. Moreover, we characterize a small population of glucose-responsive islet cells, which share the hormones and fate-determinants of both {beta}- and {delta}1-cells. The transcriptomic analysis of {beta}-cell regeneration reveals that {beta}/{delta} hybrid cells constitute a prominent source of insulin-expression during diabetes recovery. Using in vivo calcium imaging and cell tracking, we further show that the hybrid cells form de novo and acquire glucose-responsiveness in the course of regeneration. The overexpression of dkk3, a gene enriched in hybrid cells, increases their formation in the absence of {beta}-cell injury. Finally, interspecies comparison shows that plastic {delta}1-cells are partially related to PP-cells in the human pancreas. Our work provides an atlas of {beta}-cell regeneration and indicates that the rapid formation of glucose-responsive hybrid cells contributes to the resolution of diabetes in zebrafish

developmental biology↗