Table 5.

Chronological Advancements in Transcriptomic Analysis of Cryptosporidium Species.

Year	The Greatest Milestone	Outcome of Study	Reference
2011	Construction and analysis of full-length cDNA library of C. parvum	✓Cluster analysis revealed nine distinct clusters ✓Expression of transcription-related genes peaked at 2 h, proteins involved in translation dominated at 6 h, while transcripts related to structural genes, such as myosin and tubulin, were most prevalent at 12 h post-infection. An increase in transcript abundance, coinciding with the sexual reproduction of the parasites, was observed from 36 to 72 h ✓C. parvum has a more complex system of transcription regulation than previously thought	[40]
2012	CpArray15K in profiling the gene expressions in the oocysts of C. parvum and their responses to UV irradiation	✓The proteasome and ubiquitin-associated components were highly active, implying that oocysts might employ protein degradation pathways to recycle amino acids in order to overcome the inability to synthesize amino acids de novo ✓Energy metabolism in oocysts was featured by the highest level of expression of the LDH gene ✓UV irradiation of oocysts results in increased activities in cytoskeletal rearrangement and intracellular membrane trafficking	[37]
2016	New insights into the intracellular development of C. parvum	✓Identification of genes that are involved in apoptosis, cell growth, and division are differentially expressed in infected cells ✓Total of 696 genes to be differentially expressed in infected and uninfected cultured cell monolayers ✓Upregulation of host heat-shock genes and genes for Cysteine X Cysteine (CXC) chemokine	[41]
2017	Discovery of parasite RNA Transcripts delivery to infected epithelial cells during cryptosporidiosis	✓Transcripts were found to be transported into the nuclei of host epithelial cells during infection ✓Cdg7_FLc_0990 showed a unique nuclear delivery facilitated by the heat-shock protein 70-mediated nuclear import mechanism ✓Cdg7_FLc_0990 was overexpressed in intestinal epithelial cells; it led to significant changes in the expression levels of specific genes	[38]
2018	RNA-Seq insights from intestinal proliferating stages to infectious sporozoites	✓Significant differential gene expression between proliferating stages in the intestine and infectious sporozoites ✓Identification of 3774 protein-encoding transcripts in C. parvum and 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites	[43]
2019	Comparison of gene expression in the sporozoite and intracellular stages of C. parvum by RNA-Seq	✓Significant differences between the transcriptomes expressed outside and inside the host cell ✓The oocyst transcriptome is less diverse than in the host cell ✓Genes significantly overexpressed in oocysts show evidence of specialized functions not found in other Apicomplexa	[42]
2021	Analysis of Long Non-Coding RNA in C. parvum	✓A total of 396 novel lncRNAs were identified, mostly with an antisense character, of which 86% showed differential expression ✓A positive correlation between lncRNA and upstream mRNA expression was observed	[44]
2021	Transcriptome analysis of the ileocecal tissue infected with C. parvum for exploring its potential to induce digestive adenocarcinoma in a rodent model	✓Downregulation of the expression of defensin, an anti-microbial target of the parasite in response to C. parvum infection, was observed in the transformed tissues ✓Identification of immune suppressor cells and accumulation of pro-inflammatory mediators speculates that chronic inflammation induced by persistent C. parvum infection assists in the development of an immunosuppressive tumor microenvironment	[39]
2022	Whole transcriptome analysis of HCT-8 cells infected by C. parvum	✓Identification of 393 dif-lncRNAs, 69 dif-miRNAs, and 115 dif-mRNAs at 3 hpi, and 450 dif-lncRNAs, 129 dif-miRNAs, 117 dif-mRNAs, and 1 dif-circRNA at 12 hpi ✓dif-mRNAs were significantly enriched in nutritional absorption, metabolic processes, and metabolism-related pathways, while the dif-lncRNAs were mainly involved in the pathway-related and immune-related pathways ✓dif-miRNAs and dif-circRNA were significantly enriched in apoptosis and apoptosis-related pathways	[45]
2022	Dual transcriptomics to determine IFN-g-independent transcriptomic response to C. parvum infection	✓STAg treatment reduced C. parvum Iowa II oocyst shedding in IFN-g-KO mice ✓Transcripts for type I interferon-responsive genes were more abundant in C. parvum-infected mice treated with STAg ✓C. parvum transcript abundance was highest in the ileum, and mucin-like glycoproteins and the GDP-fucose transporter were among the most abundant	[47]
2023	Transcriptomic analysis of infectivity of C. hominis and C. parvum	✓C. parvum-infected cells showed higher levels of signal using Sporo-Glo™ than C. hominis-infected cells ✓Investigation of the transcriptomic landscape for the C. hominis and C. parvum assessing the gene expression of 144 host and parasite genes gene expression being at high levels, the levels of putative intracellular Cryptosporidium gene expression were low, with no significant difference from controls	[46]