Regulatory networks define phenotypic classes of human stem cell lines

Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells-typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation-to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine has highlighted the need for a general, reproducible method for classification of these cells. We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method to categorize a collection of approximately 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis we uncovered a protein-protein network (PluriNet) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks.     

Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A.

Charcot-Marie-Tooth disease 1A (CMT1A) is a hereditary demyelinating peripheral neuropathy, associated with a DNA duplication on chromosome 17p11.2. A related disorder in the mouse, trembler (Tr), maps to mouse chromosome 11 which has syntenic homology to human chromosome 17p. Recently, the peripheral myelin protein-22 (pmp-22) gene was identified as the likely Tr locus. We have constructed a partial yeast artificial chromosome contig spanning the CMT1A gene region and mapped the PMP-22 gene to the duplicated region. These observations further implicate PMP-22 as a candidate gene for CMT1A, and suggest that over-expression of this gene may be one mechanism that produces the CMT1A phenotype.     

Mite parasitism of moths: Examples of paleosymbiosis in Dominican amber

Summary Two adult moths (families Gracillariidae and Tineidae) in Dominican amber each contained a pair of larval parasitic mites attached to their bodies. The larval mites were identified as belonging to the family Erythraeidae and represent the first fossil evidence of moths parasitized by mites. Phylogenic and evolutionary implications of this find are discussed in light of similar extant associations.     

Depressor effects of muscarinic and non-muscarinic mediation induced by lateral hypothalamic stimulation in the cat

Transient sympathetically-mediated depressor effects were induced by stimulation of a small locus in the lateral hypothalamic peri-fornical region, medial to the fields of Forel. The ganglionic blocking agent, atropine methyl nitrate (ATMN), was used to show that muscarinic as well as non-muscarinic sympathetic ganglion receptor neurotransmission was involved. Evidence is presented that stimulation of this LH site co-activates a number of mechanisms and that depending on which of these are activated, the ganglionic blocking agent ATMN may either block, reverse or potentiate the depressor effect.     

On short adrenergic neurons in the accessory male genital organs of the bull

Zusammenfassung Basierend auf dem speziellen Betragen der isolierten Noradrenalingranula der inneren männlichen Geschlechtsdrüsen, die von kurzen adrenergischen Neuronen innerviert sind, werden Definitionen für 4 «übergangsformen» der peripheren katecholamin-enthaltenden Zellen diskutiert: chromaffine Zellen der Adrenomedulla, kleine verzweigte, nicht adrenale chromaffine Zellen,kurze adrenergische Neurone undlange adrenergische Neurone.     

Prostaglandin-like substances inPropionibacterium acnes. IV. Effect on isolated human vessels

Summary The present study demonstrates a powerful vasoconstrictor activity of prostaglandin-like substances (PLS), extracted fromP. acnes, on human blood vessels. PLS is about equipotent to PGE₂ in its effect on human umbilical vessels, but the contractile response pattern is different. PLS therefore seems to have specific and different physiological characteristics.     

A “SYDE” effect of hierarchical phosphorylation: possible relevance to the cystic fibrosis basic defect

The motif “SYDE”, incorporating the protein kinase CK2 consensus sequence (S-x-x-E) has been found to be phosphorylated at both its serine and tyrosine residues in several proteins. Of special interest is the case of cystic fibrosis Transmembrane-conductance Regulator (CFTR), where this motif is close to the residue (F508), whose deletion is the by far commonest cause of cystic fibrosis. Intriguingly, however, CFTR S511 cannot be phosphorylated by CK2 to any appreciable extent. Using a number of peptide substrates encompassing the CFTR “SYDE” site we have recently shown that: (1) failure of CK2 to phosphorylate the S⁵¹¹YDE motif is due to the presence of Y512; (2) CK2 readily phosphorylates S511 if Y512 is replaced by a phospho-tyrosine; (3) the Src family protein tyrosine kinase Lyn phosphorylates Y512 in a manner that is enhanced by the deletion of F508. These data, in conjunction with the recent observation that by inhibiting CK2 the degradation of F508delCFTR is reduced, lead us to hypothesize that the hierarchical phosphorylation of the motif SYDE by the concerted action of protein tyrosine kinases and CK2 is one of the mechanisms that cooperate to the premature degradation of F508delCFTR.     

Seasonal variations in the fertilizing capacity ofBufo arenarum (Amphibia Anura) spermatozoa

Resumen La capacidad fecundante de los espermatozoides deBufo arenarum decae más rápidamente en verano que en invierno. Ello probablemente sea debido a la presencia, durante el invierno, de factores testiculares de protección.

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This work was supported by a grant from the Consejo Nacional de Investigaciones Cientificas y Técnicas de la República Argentina and by the Population Council grant No. 71.68 awarded to the Consejo Nacional de Investigaciones Cientificas y Técnicas to be administered by the Instituto de Biología, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán.

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The author is most grateful to Dr.F. D. Barbieri for his kind discussion and helpful advice in the course of the present study.