PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents

Rehn, Matilda; Wenzel, Anne; Frank, Anne-Katrine; Schuster, Mikkel Bruhn; Pundhir, Sachin; Jørgensen, Nanna K.; Vitting-Seerup, Kristoffer; Ge, Ying; Jendholm, Johan; Michaut, Magali; Schoof, Erwin M.; Jensen, Tanja Lyholm; Rapin, Nicolas; Sapio, Russell T; Andersen, Kasper Langebjerg; Lund, Anders H.; Solimena, Michele; Holzenberger, Martin; Pestov, Dimitri G.; Porse, Bo T.

doi:10.1016/j.celrep.2022.110793

Cited by 5 publications

(2 citation statements)

References 83 publications

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“… 43 Similarly, repressing HSC proliferation ability will result in failed rebuilding of myeloablative hosts after transplantation, as reported by recent studies, including our own, using some gene-deficient mice, such as CDK19, Gabbr1, Ptbp1, Igf2bp2, Ptp4a, etc. 44 , 45 , 46 , 47 , 48 Therefore, it can be observed that melanocortin/MC5R axis participates in the regulation of HSC proliferation in response to stress injury.…”

Section: Discussionmentioning

confidence: 99%

Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury

et al. 2023

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Hematopoietic stem cells (HSCs) possess the great self-renewal and multidirectional differentiation ability, which contributes to the continuous generation of various blood cells. Although many intrinsic and extrinsic factors have been found to maintain HSC homeostasis, how to precisely regulate hematopoiesis under stress conditions is poorly understood. In this study, we show that melanocortin receptor 5 (MC5R) is abundantly expressed in hematopoietic stem progenitor cells (HSPCs). Using a MC5R knockout (MC5R-/-) mouse model, we observe that it is not essential for steady-state hematopoiesis. Interestingly, the levels of α-melanocyte stimulating hormone (α-MSH), an important sub-type of melanocortin, are elevated in serum and bone marrow, and the expression of MC5R is upregulated in HSPCs from mice after irradiation. MC5R deficiency aggravates irradiation-induced myelosuppression due to the impairment in the proliferation and reconstitution function of HSCs. Further investigations exhibit that melanocortin/MC5R axis regulates the proliferation of HSCs through activating the PI3K/AKT and MAPK pathways. More importantly, α-MSH treatment can significantly accelerate the hematopoietic recovery in irradiated mice. In conclusion, our data demonstrate that melanocortin/MC5R axis plays a crucial role in regulating HSC proliferation under stress, thus providing a promising strategy to promote hematopoietic regeneration when suffering from injury.

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Section: Discussionmentioning

confidence: 99%

Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury

et al. 2023

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“…Fig. S1J), a particularity found in hematopoietic stem cells in vertebrates (36) (37) (38). In addition, thanks to scRNAseq approaches, it is now possible to deduce differentiation pathways from mRNA splicing variant analysis using bioinformatic tools like Monocle3 (39).…”

Section: Tentative Model Of Hemocyte Lineages and Differentiation Pat...mentioning

confidence: 99%

Diversity and functional specialization of oyster immune cells uncovered by integrative single cell level investigations

de La Forest Divonne,

Pouzadoux,

Romatif

et al. 2024

Preprint

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Mollusks constitute a large part of the animal biodiversity and play an important role in ecosystems and global food security. The Pacific oyster, Crassostrea (Magallana) gigas, is the most farmed bivalve mollusk in the world and has become a model species. Despite the number of studies on bivalves' immune cells, the hemocytes, their characterization remains elusive. By using a combination of single-cell RNA sequencing, quantitative cytology, functional assays and trajectory analyses, we characterized a total of seven distinct hemocyte types and defined at least three hematopoietic lineages. This integrative analysis allowed us to reconcile molecular and cellular data and identify cell types performing specific immune functions such as phagocytosis, ROS production, copper accumulation, and expression of antimicrobial peptides. These findings pave the way for a deeper understanding of key physiological and immune responses, to help develop mitigation strategies, limit the impact of disease and to contribute to the sustainability of bivalve farming.

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PTBP1 controls intestinal epithelial regeneration through post-transcriptional regulation of gene expression

Chembazhi

Tung

Hwang

et al. 2023

Nucleic Acids Research

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The intestinal epithelial regeneration is driven by intestinal stem cells under homeostatic conditions. Differentiated intestinal epithelial cells, such as Paneth cells, are capable of acquiring multipotency and contributing to regeneration upon the loss of intestinal stem cells. Paneth cells also support intestinal stem cell survival and regeneration. We report here that depletion of an RNA-binding protein named polypyrimidine tract binding protein 1 (PTBP1) in mouse intestinal epithelial cells causes intestinal stem cell death and epithelial regeneration failure. Mechanistically, we show that PTBP1 inhibits neuronal-like splicing programs in intestinal crypt cells, which is critical for maintaining intestinal stem cell stemness. This function is achieved at least in part through promoting the non-productive splicing of its paralog PTBP2. Moreover, PTBP1 inhibits the expression of an AKT inhibitor PHLDA3 in Paneth cells and permits AKT activation, which presumably maintains Paneth cell plasticity and function in supporting intestinal stem cell niche. We show that PTBP1 directly binds to a CU-rich region in the 3′ UTR of Phlda3, which we demonstrate to be critical for downregulating the mRNA and protein levels of Phlda3. Our results thus reveal the multifaceted in vivo regulation of intestinal epithelial regeneration by PTBP1 at the post-transcriptional level.

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PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents

Cited by 5 publications

References 83 publications

Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury

Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury

Diversity and functional specialization of oyster immune cells uncovered by integrative single cell level investigations

PTBP1 controls intestinal epithelial regeneration through post-transcriptional regulation of gene expression

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