Hematopoietic Stem Cell Transcription Factors in Cardiovascular Pathology

Duddu, Sushmitha; Chakrabarti, Rituparna; Ghosh, Anuran; Shukla, Praphulla Chandra

doi:10.3389/fgene.2020.588602

Cited by 6 publications

(3 citation statements)

References 327 publications

(346 reference statements)

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“…GO term analysis of these target genes showed a number of remarkably linked to GO terms associated with transcription, phosphorylation, development and angiogenesis. Multiple genetic disorders, mainly metabolic and cardiovascular diseases are associated with transcription of metabolism-associated genes [ 29 ]. Protein phosphorylation is a key signaling mechanism for regulating cellular pathways implicated in several physiological processes associated with cardiovascular and metabolic systems in the body [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Profiling of exosomal microRNAs expression in umbilical cord blood from normal and preeclampsia patients

Pan

Shi

Fang

et al. 2022

BMC Pregnancy Childbirth

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Background Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies. Methods A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum. Results Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P<0.05, log2|FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes. Conclusion The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Profiling of exosomal microRNAs expression in umbilical cord blood from normal and preeclampsia patients

Pan

Shi

Fang

et al. 2022

BMC Pregnancy Childbirth

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“…Its homeostasis is regulated by a complex set of external signals and intrinsic fate determinants. Among those, transcription factors (TFs) have been shown to play a central role in regulating hematopoiesis, particularly by influencing the self-renewal and differentiation of HSCs through orchestrating the coordinated expression of target genes as lineage establishment begins and progresses ( 110 ).…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies

2023

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The functionality and longevity of hematopoietic tissue is ensured by a tightly controlled balance between self-renewal, quiescence, and differentiation of hematopoietic stem cells (HSCs) into the many different blood lineages. Cell fate determination in HSCs is influenced by signals from extrinsic factors (e.g., cytokines, irradiation, reactive oxygen species, O2 concentration) that are translated and integrated by intrinsic factors such as Transcription Factors (TFs) to establish specific gene regulatory programs. TFs also play a central role in the establishment and/or maintenance of hematological malignancies, highlighting the need to understand their functions in multiple contexts. TFs bind to specific DNA sequences and interact with each other to form transcriptional complexes that directly or indirectly control the expression of multiple genes. Over the past decades, significant research efforts have unraveled molecular programs that control HSC function. This, in turn, led to the identification of more than 50 TF proteins that influence HSC fate. However, much remains to be learned about how these proteins interact to form molecular networks in combination with cofactors (e.g. epigenetics factors) and how they control differentiation, expansion, and maintenance of cellular identity. Understanding these processes is critical for future applications particularly in the field of cell therapy, as this would allow for manipulation of cell fate and induction of expansion, differentiation, or reprogramming of HSCs using specific cocktails of TFs. Here, we review recent findings that have unraveled the complexity of molecular networks controlled by TFs in HSCs and point towards possible applications to obtain functional HSCs ex vivo for therapeutic purposes including hematological malignancies. Furthermore, we discuss the challenges and prospects for the derivation and expansion of functional adult HSCs in the near future.

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“…It is also the paradigm of mammalian tissue homeostasis, sustained by hematopoietic stem and progenitor cells (HSPCs) over the lifetime of an organism. Transcription factors (TFs) have a central role in regulating hematopoiesis, particularly by impacting HSPC self-renewal and differentiation through the orchestration of coordinated expression of target genes as lineage commitment initiates and progresses [2]. Single-cell genomics has provided unprecedented insights into the regulatory heterogeneity in individual cells, and multiple methods have been developed to predict upstream regulators of the transcriptional programs of specific cell states along the course of differentiation [3].…”

Section: Introductionmentioning

confidence: 99%

Deciphering transcriptional and functional heterogeneity in hematopoiesis with single-cell genomics

Martin-Rufino

Sankaran

2021

Current Opinion in Hematology

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Purpose of review Single-cell genomic approaches have uncovered cell fate biases and heterogeneity within hematopoietic subpopulations. However, standard single-cell transcriptomics suffers from high sampling noise, which particularly skews the distribution of lowly expressed genes, such as transcription factors (TFs). This might preclude the identification of rare transcripts that define cell identity and demarcate cell fate biases. Moreover, these studies need to go hand in hand with relevant functional assays to ensure that observed gene expression changes represent biologically meaningful alterations. Recent findings Single-cell lineage tracing and functional validation studies have uncovered cell fate bias within transcriptionally distinct hematopoietic stem and progenitor subpopulations. Novel markers identified using these strategies have been proposed to prospectively isolate functionally distinct subpopulations, including long-term hematopoietic stem cells for ex vivo applications. Furthermore, the continuous nature of hematopoiesis has prompted the study of the relationship between stochastic transcriptional noise in hematopoietic TFs and cell fate determination. Summary An understanding of the limitations of single-cell genomic approaches and follow-up functional assays is critical to discern the technical and biological contribution of noise in hematopoietic heterogeneity, to identify rare gene expression states, and to uncover functionally distinct subpopulations within hematopoiesis. Supplementary video http://links.lww.com/COH/A23

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Hematopoietic Stem Cell Transcription Factors in Cardiovascular Pathology

Cited by 6 publications

References 327 publications

Profiling of exosomal microRNAs expression in umbilical cord blood from normal and preeclampsia patients

Profiling of exosomal microRNAs expression in umbilical cord blood from normal and preeclampsia patients

Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies

Deciphering transcriptional and functional heterogeneity in hematopoiesis with single-cell genomics

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