Impact of the Megakaryocytic Vascular Niche on Platelet Biogenesis

Schulze, Harald; Semeniak, Daniela; Balduini, Alessandra

doi:10.1007/978-3-319-39562-3_4

Cited by 2 publications

(3 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also show that LGR5 expression is heterogeneous in bud tip cells in areas of high RSPO2 expression. That, combined with their position in the fetal airway bud tips, and previous reports that LGR5 itself in the intestinal crypts is correlated with anchoring in a niche (55), suggests that LGR5 may be important for directing tube elongation, controlling lung airway growth, and maintaining an undifferentiated state as the bud tips elongate throughout development. In the adult, epithelial LGR5 expression is absent, yet it's reactivated during bronchioalveolar organoid formation suggesting that this transient pathway may be reactivated during regeneration.…”

Section: Discussionmentioning

confidence: 58%

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

Polkoff

Gupta

Murphy

et al. 2022

Preprint

View full text Add to dashboard Cite

Stem cells play a pivotal role in lung homeostasis, repair, and regeneration, and yet the mechanisms underlying these processes are unknown. Furthermore, species-specific differences make certain findings from mice, a widely used animal model, difficult to translate into humans. In this work, we address these limitations by using a transgenic pig model and identify two populations of LGR5+ cells in the lung. Interestingly, we found similar populations in human lungs but not in mice. Using RNA sequencing, 3D imaging, organoid models, and differentiation assays, we determine that in the fetal lung, epithelial LGR5 expression is transient in a subpopulation of developing lung bud tips, co-expresses bud tip markers SOX9 and SFTPC. While epithelial LGR5 expression is absent from postnatal lung, it is reactivated in bronchioalveolar organoids derived from basal airway cells. A separate population of LGR5+ cells is mesenchymal, surrounds developing and mature airways, lies adjacent to airway basal cells, is closely associated with nerve fibers, and acts as a multipotent progenitor cell capable of supporting the airway basal cell niche. Transcriptionally, mesenchymal LGR5+ cells are analogous to stromal stem cell populations and express unique patterns of WNT and TGFbeta signaling pathway genes. These results point to two roles for LGR5 in orchestrating stem and progenitor cell dynamics and provide a physiologically relevant model for further studies on the role of these populations in repair and regeneration.

show abstract

Section: Discussionmentioning

confidence: 58%

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

Polkoff

Gupta

Murphy

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Existing literature also supported our research interest towards this miRNA. In fact, several lines of evidence are indicative of a link between miR1202, GATA-1 and leukaemia: (i) miR-1202 has been firstly isolated from leukaemia cells [55]; (ii) miR-1202 is encoded at locus 6q25.3, a cancer-associated genomic region involved in (6,21) translocation in acute myeloid leukaemia [56][57][58]; (iii) miR-1202 has a well-documented tumour suppressive role in different tumour tissues as it has been found downregulated in glioma, ovarian cancer and clear cell papillary renal carcinoma cells [41,59,60].…”

Section: Discussionmentioning

confidence: 99%

“…The shorter isoform can originate either from an alternatively spliced mRNA variant lacking exon 2 or from the use of an alternative translation initiation site (Met84) located in exon 3 (figure 1) [1][2][3]. These two isoforms have distinct roles in normal haematopoiesis: as the result of a complex interplay of transcriptional networks, GATA-1 FL promotes the terminal differentiation of megakaryocytic-erythroid lineages, whereas GATA-1 S enhances the proliferation and self-renewal of myeloid progenitors and contributes to the maintenance of the proliferative potency of haematopoietic precursors and skewing of the myeloid lineage [1][2][3][4][5][6][7][8][9]. Consequently, an imbalanced expression of GATA-1 S over GATA-1 FL has been identified as an oncogenic factor in several haematopoietic disorders including different subtypes of acute and chronic myeloid leukaemia [3,[10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

Sessa,

Trombetti,

Bianco

et al. 2024

Open Biol.

View full text Add to dashboard Cite

Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1 S ). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1 S , we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1 S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1 S . These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1 S levels.

show abstract

Impact of the Megakaryocytic Vascular Niche on Platelet Biogenesis

Cited by 2 publications

References 116 publications

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

Contact Info

Product

Resources

About

Impact of the Megakaryocytic Vascular Niche on Platelet Biogenesis

Cited by 2 publications

References 116 publications

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 S expression

Contact Info

Product

Resources

About

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression