Biomedical subjects

Amélie Faubert

Publications and source records attributed to Amélie Faubert.

3 recordsLinked to original sources

PubMed2004

Genetic programs regulating HSC specification, maintenance and expansion.

All mature blood cells originate from a small population of self-renewing pluripotent hematopoietic stem cells (HSCs). The capacity to self-renew characterizes all stem cells, whether normal or neoplastic. Interestingly, recent studies suggest that self-renewal is essential for tumor cell maintenance, implicating that this process has therapeutic relevance. Unfortunately, the molecular bases for self-renewal of vertebrate cells remain poorly defined. This article will focus on the developmental mechanisms underlying fetal and adult HSC homeostasis. Specifically, distinctions between genetic programs regulating HSC specification (identity), self-renewal (in both fetal and adult) and differentiation/commitment will be discussed with a special emphasis on transcriptional and chromatin regulators.

Acute Disease↗

PubMed2004

Are genetic determinants of asymmetric stem cell division active in hematopoietic stem cells?

Stem cells have acquired a golden glow in the past few years as they represent possible tools for reversing the damage wreak on organs. These cells are found not only in major regenerative tissues, such as the epithelia, blood and testes, but also in 'static tissues', such as the nervous system and liver, where they play a central role in tissue growth and maintenance. The mechanism by which stem cells maintain populations of highly differentiated, short-lived cells seems to involve a critical balance between alternate fates: daughter cells either maintain stem cell identity or initiate differentiation. Recent studies in lower organisms have unveiled the regulatory mechanisms of asymmetric stem cell divisions. In these models, the surrounding environment likely provides key instructive signals for the cells to choose one fate over another. Our understanding now extends to the intrinsic mechanisms of cell polarity that influence asymmetrical stem cell divisions. This article focuses on the genetic determinants of asymmetric stem cell divisions in lower organisms as a model for studying the process of self-renewal of mammalian hematopoietic stem cells.

Animals↗

PubMed2001

Functional analysis of tryptophans alpha 62 and beta 120 on HLA-DM.

In the endocytic pathway of antigen-presenting cells, HLA-DM catalyzes the exchange between class II-associated invariant chain peptide (CLIP) and antigenic peptides onto major histocompatibility complex class II molecules. At low pH of lysosomal compartments, both HLA-DM and HLA-DR undergo conformational changes, and it was recently postulated that two partially exposed tryptophans on HLA-DM might be involved in the interaction between the two molecules. To define contact regions on HLA-DM, we have conducted site-directed mutagenesis on those two hydrophobic residues. The HLA-DM alphaW62A,betaW120A (DM(W62A/W120A)) double mutant was expressed in HLA-DR(+) HeLa cells expressing invariant chain, and the activity of this DM molecule was assessed. Flow cytometry analysis of cell surface DR-CLIP complexes revealed that DM(W62A/W120A) removes CLIP as efficiently as its wild-type counterpart. DM(W62A/W120A) was found in the endocytic pathway by immunofluorescence, and DM-DR complexes were immunoprecipitated from these cells at pH 5. Finally, mutations alphaW62A and betaW120A on HLA-DM did not affect the association with HLA-DO. The complex egresses the endoplasmic reticulum and accumulates in endocytic vesicles. Moreover, DO and DM(W62A/)W120A were co-immunoprecipitated at pH 7. We conclude that the alpha62 and beta120 tryptophan residues are not required for the activity of DM, nor are they directly implicated in the interaction with DR or DO.

Blotting, Western↗