Biology subjects

Ferdous, A. S.

Publications and source records attributed to Ferdous, A. S..

3 recordsLinked to original sources

bioRxiv2026

Transcriptomic profiling identifies cellular and molecular transitions during Merkel cell regeneration

Skin exhibits a remarkable capacity for regeneration, which requires the coordinated reconstitution of diverse cell types and structures. Merkel cells are mechanosensory cells that detect gentle touch and develop in coordination with dermal appendages, yet Merkel cell regeneration remains incompletely understood. To investigate Merkel cell lineage dynamics during skin regeneration, we performed single-cell RNA sequencing of regenerating adult zebrafish skin after dermal appendage removal. We find that the regenerating Merkel cell lineage is heterogeneous and characterize molecular markers associated with Merkel cell subpopulations. Through cross-species analysis with mouse and human Merkel cells, we identify conserved elements of Merkel cell identity and function across vertebrates. Trajectory analysis reveals a continuous spectrum of transcriptional state transitions within the Merkel cell population, suggesting dynamic lineage progression during regeneration and involving an epithelial-to-mesenchymal-like transition. Finally, cell fate mapping and in vivo analysis identify a putative pool of cldna+ suprabasal keratinocyte progenitors that give rise to regenerating Merkel cells. Together, these findings establish a genome resource for studies of zebrafish skin regeneration and provide insights into Merkel cell heterogeneity, conservation, lineage relationships and regenerative dynamics.

developmental biology↗

bioRxiv2023

Functional significance of PUF partnerships in C. elegans germline stem cells

PUF RNA-binding proteins are conserved stem cell regulators. Four PUF proteins govern self-renewal of C. elegans germline stem cells together with two intrinsically disordered proteins, LST-1 and SYGL-1. Based on yeast two-hybrid results, we proposed a composite self-renewal hub in the stem cell regulatory network, with eight PUF partnerships and extensive redundancy. Here, we investigate LST-1-PUF and SYGL-1-PUF partnerships and their molecular activities in their natural context - nematode stem cells. We confirm LST-1-PUF partnerships and their specificity to self-renewal PUFs by co-immunoprecipitation and show that an LST-1(AmBm) mutant defective for PUF-interacting motifs does not complex with PUFs in nematodes. LST-1(AmBm) is used to explore the functional significance of the LST-1-PUF partnership. Tethered LST-1 requires the partnership to repress expression of a reporter RNA, and LST-1 requires the partnership to co-immunoprecipitate with NTL-1/Not1 of the CCR4-NOT complex. We suggest that the partnership provides multiple molecular interactions that work together to form an effector complex on PUF target RNAs. Comparison of PUF-LST-1 and Pumilio-Nanos reveals fundamental molecular differences, making PUF-LST-1 a distinct paradigm for PUF partnerships. Summary statementPartnerships between PUF RNA-binding proteins and intrinsically disordered proteins are essential for stem cell maintenance and RNA repression.

developmental biology↗

bioRxiv2019

LST-1 acts in trans with a conserved RNA-binding protein to maintain stem cells

Stem cell self-renewal is essential to development and tissue repair. The C. elegans LST-1 protein is a pivotal regulator of self-renewal and oncogenic when misexpessed. Here we define regions within the LST-1 protein that provide molecular insights into both its function and regulation. LST-1 self-renewal activity resides within a predicted disordered region that harbors two KXXL motifs. These KXXL motifs mediate LST-1 binding to FBF, a broadly conserved Pumilio/PUF RNA-binding protein that represses differentiation. Point mutations of the KXXL motifs abrogate LST-1 self-renewal activity. Therefore, FBF binding is essential to LST-1 function. A second distinct region regulates LST-1 spatial expression and primarily affects LST-1 protein turnover. Upon loss of this regulatory region, LST-1 protein distribution expands and drives formation of a larger than normal GSC pool. Thus, LST-1 promotes self-renewal as a key FBF partner, and its spatial regulation helps determine size of the GSC pool.\n\nIMPACT STATEMENTA key stem cell regulator partners with a broadly conserved PUF RNA-binding protein to drive self-renewal and maintain a stem cell pool.

developmental biology↗