Insulin-like growth factor 2 modulates murine hematopoietic stem cell maintenance through upregulation of p57

Thomas, Dylan C.; Sommer, Andreia Gianotti; Balazs, Alejandro B.; Beerman, Isabel; Murphy, George J.; Rossi, Derrick J.; Mostoslavsky, Gustavo

doi:10.1016/j.exphem.2016.01.010

Cited by 19 publications

(30 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, Igf2 overexpression would boost HSC progression into the cell cycle, leading to proliferation with a risk of exhaustion of the HSC pool on the long term. The data of Thomas et al 2016 show that in this situation p57 increases and limits the progression of HSC through the cell cycle, preserving the HSC pool and a better repopulation capacity. Our two studies suggest that p57 would counterbalance the effects of Igf2 on the HSC pool in order to protect it.…”

Section: Discussionmentioning

confidence: 99%

Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood

Barroca¹,

Lewandowski²,

Jaracz‐Ros³

et al. 2017

EBioMedicine

View full text Add to dashboard Cite

Insulin-like Growth Factor 2 (IGF2) belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC) successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span.

show abstract

Section: Discussionmentioning

confidence: 99%

Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood

Barroca¹,

Lewandowski²,

Jaracz‐Ros³

et al. 2017

EBioMedicine

View full text Add to dashboard Cite

show abstract

“…To further explore the nature of this developmental transition, we searched for DEGs that were concurrently downregulated in all stromal lineages in adult compared to juvenile BM. We found a unique signature containing only seven common genes, which includes Ptn, Igf2 and Dlk1, genes that are known to play decisive roles in the regulation of self-renewing expansion of adult and embryonic (Chou and Lodish, 2010;Himburg et al, 2018;Kokkaliaris et al, 2016;Mascarenhas et al, 2009;Thomas et al, 2016) HSCs . Strikingly, all seven genes displayed by far the highest expression levels in juvenile PαSc compared to other stromal subsets, and the majority (four out of seven, Igf2, Dlk1, Peg3 and Mest) belong to a group of genomically imprinted genes, which are monoallelicaly expressed in a parent of origin-specific fashion ( Figure 4E).…”

mentioning

confidence: 89%

“…Among them, IGF2 is a mitogenic factor for HSCs, which is produced by putative niche cell types of the fetal liver (Chou and Lodish, 2010;Mascarenhas et al, 2009;Thomas et al, 2016;Wu et al, 2008).…”

mentioning

confidence: 99%

Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging and inflammation

Helbling

Piñeiro-Yáñez

Gerosa

et al. 2019

Preprint

View full text Add to dashboard Cite

Bone marrow (BM) stromal cells provide the structural and regulatory framework for hematopoiesis and contribute to developmental-stage specific niches, such as those preserving hematopoietic stem cell (HSCs). Despite recent advances in our understanding of stromal composition and function, little is known on the dynamic transcriptional remodeling that this compartment undergoes over time and during adaptation to stress. Similarly, how molecular changes in stroma are linked to age-related modulation of hematopoiesis is poorly understood. Using RNA-sequencing, we performed a longitudinal comparison of the transcriptional profile of four principal mesenchymal and endothelial stromal subsets, namely CXCL12-abundant reticular (CARc), PDGFR-α + Sca-1 + , sinusoidal (SECs) and arterial endothelial cells (AECs), isolated from early postnatal, adult and aged mice. Our data i) provide molecular fingerprints defining novel, cell-specific anatomical and functional features ii) reveal radical reprogramming of pro-hematopoietic, immune and matrisomic transcriptional programs during the narrow temporal transition from juvenile to adult stages iii) demonstrate that homeostatic aging is characterized by a progressive and pronounced upregulation of pro-inflammatory gene-expression and loss of stromal cell fitness. By profiling in vivo responses of stromal cells to infection-mimicking agents, we finally demonstrate that transcriptomic pathways elicited by sterile inflammation are largely recapitulated during aging, thereby supporting the inflammatory basis of aging-related adaptations of BM hematopoietic function. Transcriptomic profiling of BM stroma Helbling et al.

show abstract

“…Culturing hematopoietic stem cells with IGF2 increases the number of both multilineage colonies and hematopoietic stem cells (Zhang & Lodish ; Thomas et al . ). We also found that 12.5, 14.5 and 16.5 dpc liver hepatoblast‐like cells highly express Igf2 mRNA (Figs S2–S4 in Supporting Information).…”

Section: Discussionmentioning

confidence: 97%

“…Taken together, hepatic stellate cells likely function as hematopoietic niche through Igf2 secretion. IGF2 is expressed in long-term hematopoietic stem cells and produced by 15 dpc Ter119-CD3+ fetal liver cells (Zhang & Lodish 2004;Thomas et al 2016). Culturing hematopoietic stem cells with IGF2 increases the number of both multilineage colonies and hematopoietic stem cells (Zhang & Lodish 2004;Thomas et al 2016).…”

Section: 82mentioning

confidence: 99%

Expression of cytokine and extracellular matrix mRNAs in fetal hepatic stellate cells

et al. 2017

View full text Add to dashboard Cite

In mouse fetal liver, hepatoblasts, sinusoidal endothelial cells and macrophages (or erythroblastic islands) promote differentiation and proliferation of hematopoietic cells through cell-cell interactions and secretion of cytokines and extracellular matrix factors. Until now, we have had little knowledge of the hematopoietic cytokines or extracellular matrix mRNAs expressed in hepatic stellate cells. Using p75 neurotrophin receptor (p75NTR) to mark this cell population, we sorted 12.5, 14.5 and 16.5 dpc hepatic stellate cells and analyzed expression of cytokines and extracellular matrix mRNAs. Among cytokines, insulin-like growth factor 2 (Igf2) was highly expressed at all three stages analyzed. The extracellular matrix molecule fibronectin (Fn1) was highly expressed in 12.5 dpc cells, whereas vitronectin (Vtn) was highly expressed in 14.5 and 16.5 dpc hepatic stellate cells. Among liver cells, Igf2 was predominantly expressed in hepatoblast-like cells at all three stages examined, suggesting that hepatoblast-like cells are an essential part of the niche that maintains homeostasis of hematopoietic cells in embryonic mouse liver. Defining these expression patterns could facilitate our understanding of cross talk between cytokine and extracellular matrix molecules in hepatic stellate cells and benefit research in developmental hematopoiesis as well as the study of liver biology.

show abstract

Insulin-like growth factor 2 modulates murine hematopoietic stem cell maintenance through upregulation of p57

Cited by 19 publications

References 58 publications

Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood

Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood

Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging and inflammation

Expression of cytokine and extracellular matrix mRNAs in fetal hepatic stellate cells

Contact Info

Product

Resources

About