Biology subjects

Naiyer, S.

Publications and source records attributed to Naiyer, S..

4 recordsLinked to original sources

bioRxiv2026

miRNA-mediated regulation of lineage plasticity in YY1 knockout pro-B cells

Yin Yang 1 (YY1) is a multifunctional transcription factor involved in chromatin organization and gene regulation. While the mechanisms by which YY1 controls B cell lineage development have been explored at the transcriptional level, little is known at the post-transcriptional level. To address this, we performed integrated analyses combining bulk transcriptomics, miRNA profiling, and single-cell transcriptomics to identify YY1-dependent regulatory networks at the pro-B cell stage. YY1 knockout (KO) in pro-B cells leads to reduced B-lineage commitment and activation of genes associated with alternative hematopoietic fates. Our integrative analyses suggest that these changes are organized in part through coordinated miRNA-mRNA regulatory networks. In wild-type (WT) pro-B cells, miRNAs such as miR-10a-5p, miR-674-5p, and miR-21a-5p maintain B cell identity by suppressing RNAs linked to other lineages. In contrast, in YY1 KO pro-B cells increased expression of miRNAs including miR-15b-5p, miR-342-5p, and miR-34a-5p target pathways required for B cell development, proliferation, and survival thus reducing B lineage identity. Together, these findings suggest that YY1 preserves B cell identity through coordinated regulation of transcriptional and post-transcriptional programs, with YY1-dependent miRNA networks contributing to the maintenance of B cell-associated gene expression and restriction of alternative lineage programs. Among these, miR-15b-5p emerged as a central regulator predicted to regulate Bcl6b and E2f family transcription factors that control proliferative and transcriptional programs critical for early B cell development. At single-cell resolution, YY1 KO pro-B cells grown on OP9-DL4 feeders that provide Notch signaling displayed marked transcriptional heterogeneity and loss of pro-B lineage commitment. Pseudotime analysis revealed a branched developmental landscape, with cells diverging toward monocyte, macrophage, and dendritic cell fates rather than a consistent B cell differentiation trajectory. Collectively, these findings establish YY1 as a central regulator of lineage commitment integrating transcriptional and miRNA-mediated post-transcriptional mechanisms to regulate B cell identity.

molecular biology↗

bioRxiv2024

Unusual lineage plasticity revealed by YY1 knockout in pro-B cells

During B cell development, cells progress through multiple developmental stages with the pro-B cell stage defining commitment to the B cell lineage. YY1 is a ubiquitous transcription factor that is capable of both activation and repression functions. We find here that knockout of YY1 at the pro-B cell stage eliminates B lineage commitment. YY1 knockout pro-B cells can generate T lineage cells in vitro using the OP9- DL4 feeder system, as well as in vivo after injection into sub-lethally irradiated Rag1-/- mice. These T lineage-like cells lose their B lineage transcript profile and gain a T cell lineage profile. Single cell-RNA-seq experiments showed that as YY1 knockout pro-B cells transition into T lineage cells, various cell clusters adopt transcript profiles representing a multiplicity of hematopoietic lineages indicating unusual lineage plasticity. Given the ubiquitous nature of YY1 and its dual activation and repression functions, YY1 likely regulates commitment in multiple cell lineages.

developmental biology↗

bioRxiv2021

Transcriptomic analysis of ribosome biogenesis and pre-rRNA processing during growth stress in Entamoeba histolytica

Ribosome biogenesis, a multi-step process involving the transcription, modification, folding and processing of rRNA is the major consumer of cellular energy. It involves the sequential assembly of ribosomal proteins (RP)s via more than 200 ribogenesis factors. Unlike model organisms where transcription of rRNA and RP genes slows down during stress, in Entamoeba histolytica, pre-rRNA synthesis continues, and unprocessed pre-rRNA accumulates. To gain insight into the vast repertoire of ribosome biogenesis factors and understand the major components playing role during stress we computationally identified the ribosome biogenesis factors in E. histolytica. Of the total [~]279 S. cerevisiae proteins, we could only find 188 proteins in E. histolytica. Some of the proteins missing in E. histolytica were also missing in humans. A number of proteins represented by multiple genes in S. cerevisiae had only a single copy in E. histolytica. It was interesting to note that E. histolytica lacked mitochondrial ribosome biogenesis factors and had far less RNase components as compared to S. cerevisiae. Northern hybridization using probes from different spacer regions depicted the accumulation of unprocessed intermediates during stress. Transcriptomic studies revealed the differential regulation of a number of ribosomal factors both in serum-starved and RRP6KD conditions. The ARB1 protein involved at multiple steps of ribosome biogenesis and NEP1 and TSR3 involved in chemical modification of 18S rRNA previously shown to accumulate pre-rRNA precursors upon downregulation in S. cerevisiae and humans were included. The data reveals the importance of some of the major factors required for regulating pre-rRNA processing during stress. This is the first report on the complete repertoire of ribosome biogenesis factors in E. histolytica.

microbiology↗

bioRxiv2020

Ultra-structural analysis and morphological changes during the differentiation of trophozoite to cyst in Entamoeba invadens

Entamoeba Histolytica, a pathogenic parasite, is the causative organism of amoebiasis and uses human colon to complete its life cycle. It destroys intestinal tissue leading to invasive disease. Since it does not form cyst in culture medium, a reptilian parasite Entamoeba invadens serves as the model system to study encystation. Detailed investigation on the mechanism of cyst formation, information on ultra-structural changes and cyst wall formation during encystation are still lacking in E. invadens. Here, we used electron microscopy to study the ultrastructural changes during cyst formation and showed that the increase in heterochromatin patches and deformation of nuclear shape were early events in encystation. These changes peaked at ~20h post induction, and normal nuclear morphology was restored by 72h. Two types of cellular structures were visible by 16h. One was densely stained and consisted of the cytoplasmic mass with clearly visible nucleus. The other consisted of membranous shells with large vacuoles and scant cytoplasm. The former structure developed into the mature cyst while the latter structure was lost after 20h, This study of ultra-structural changes during encystation in E. invadens opens up the possibilities for further investigation into the mechanisms involved in this novel process.

cell biology↗