Metatason ohjeistus onnistuneeseen käyttäjäkokemukseen talouslukutaitoa opettavissa tietojärjestelmissä

Talouslukutaidon merkitys kasvaa maailman digitalisoituessa. Kuluttajille on tarjolla yhä useampia tapoja erilaisiin rahoitustuotteisiin. Lainaa on yhä helpompi ottaa, erilaisten kulutusluottojen määrä on kasvanut, ja yksilön vastuu omasta taloudesta on korostunut. Samaan aikaan myös normaalista kuluttamisesta on tullut helpompaa. Verkkokaupat sallivat ostosten tekemisen muutamalla hiiren klikkauksella, ja on useita erilaisia kuukausimaksullisia palveluita, joiden hintaa ei välttämättä käsitä arjen muiden menojen joukossa. Tämän vastapainoksi taloudellista opetusta ei juuri tapahdu Suomessa peruskoulun jälkeen. Web-pohjaisia ratkaisuja talouden opettamiseen on vain muutamia ja niiden käyttäjäkokemuksessa on selviä puutteita. Kansalaisten vaihtoehdot taloudellisen osaamisen opiskelulle ovat siis vähäiset. Suomessa tulisi olla tietojärjestelmä, joka takaa kaikille laadukasta taloudellista opetusta. Tässä tutkimuksessa käsitellään onnistunutta käyttäjäkokemusta talouslukutaitoa opettavissa tietojärjestelmissä. Tutkimuksen tavoitteena oli kehittää suunnittelutieteiden avulla artefakti, jonka avulla voidaan suunnitella onnistuneen käyttäjäkokemuksen omaavia talouslukutaitoja opettavia tietojärjestelmiä. Tutkimuksen tutkimuskysymykseksi asetettiin: Millainen metatason ohjeistus johtaa onnistuneeseen käyttäjäkokemukseen talouslukutaitoa kehittävässä tietojärjestelmässä. Tutkielman tutkimusmenetelmänä oli suunnittelutiede, jonka iteratiivisen prosessin kautta luotiin artefakti, metatason ohjeistus. Artefaktin tietopohja pohjautuu käyttäjäkokemuksen ja talouslukutaidon aiempien tutkimusten teorioihin, määrittelyihin ja suunnittelun viitekehyksiin. Artefaktin relevanttius varmistettiin havaitsemalla ongelma vallitsevasta talouslukutaidon opetuksen ympäristöstä. Tästä tietopohjasta muodostettiin ohjeistus, joka johtaa onnistuneeseen käyttäjäkokemukseen tietojärjestelmässä, jonka tarkoitus on kehittää käyttäjien taloudellista osaamista. Ohjeistusta demonstroitiin uuden pelkistetyn tietojärjestelmän luonnilla konseptitasolla. Demonstraation avulla kuvattiin ohjeistuksen käyttöä käytännössä ja arvioitiin ohjeistuksen käyttökelpoisuutta tietojärjestelmän kehitysprosessissa. Tutkimuksen tuloksena tuotettiin kymmenen ohjeen ohjeistus, jossa käyttäjäkeskeisen ja käyttäjäkokemuksen suunnittelun periaatteet ovat mukana. Metatason ohjeistuksessa määritellään ensin tavoiteltujen käyttäjien tarpeet ja sen jälkeen siirrytään ohje ohjeelta abstrakteista konseptimääritelmistä konkreettisiin osiin suunniteltavaa järjestelmää ja lopuksi jatkuvaan käytettävyyden ja käyttäjäkokemuksen arviointiin. Ohjeistuksessa korostuu käyttäjien tarpeiden täyttäminen, suunnittelun ja jatkuvan käyttäjäkokemuksen arvioinnin kautta. Lisäksi erityispaino asetettiin saavutettavuudelle sekä luotettavuudelle käyttäjäkokemuksen kannalta. Talouslukutaidon opetuksen muotoon ei oteta ohjeistuksessa kantaa. Ohjeistusta voidaan soveltaa tietojärjestelmän suunnittelun aloituksesta tietojärjestelmän kehittämisen loppuun asti. Lisäksi ohjeistusta voidaan soveltaa minkä vain tuotteen suunnittelussa sekä kehittämisessä pitäen käyttäjäkokemuksen keskeisenä tekijänä tuotteen suunnittelussa

FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner

Fibroblast growth factor 8 (FGF8), acting through the fibroblast growth factor receptor 1 (FGFR1), has an important role in the development of gonadotropin-releasing hormone-expressing neurons (GnRH neurons). We hypothesized that FGF8 regulates differentiation of human GnRH neurons in a time-and dose-dependent manner via FGFR1. To investigate this further, human pluripotent stem cells were differentiated during 10 days of dual-SMAD inhibition into neural progenitor cells, followed either by treatment with FGF8 at different concentrations (25 ng/ml, 50 ng/ml or 100 ng/ml) for 10 days or by treatment with 100 ng/ml FGF8 for different durations (2, 4, 6 or 10 days); cells were then matured through DAPT-induced inhibition of Notch signaling for 5 days into GnRH neurons. FGF8 induced expression of GNRH1 in a dose-dependent fashion and the duration of FGF8 exposure correlated positively with gene expression of GNRH1 (PPeer reviewe

Distinct differentiation characteristics of individual human embryonic stem cell lines

BACKGROUND: Individual differences between human embryonic stem cell (hESC) lines are poorly understood. Here, we describe the derivation of five hESC lines (called FES 21, 22, 29, 30 and 61) from frozen-thawed human embryos and compare their individual differentiation characteristic. RESULTS: The cell lines were cultured either on human or mouse feeder cells. The cells grew significantly faster and could be passaged enzymatically only on mouse feeders. However, this was found to lead to chromosomal instability after prolonged culture. All hESC lines expressed the established markers of pluripotent cells as well as several primordial germ cell (PGC) marker genes in a uniform manner. However, the cell lines showed distinct features in their spontaneous differentiation patterns. The embryoid body (EB) formation frequency of FES 30 cell line was significantly lower than that of other lines and cells within the EBs differentiated less readily. Likewise, teratomas derived from FES 30 cells were constantly cystic and showed only minor solid tissue formation with a monotonous differentiation pattern as compared with the other lines. CONCLUSION: hESC lines may differ substantially in their differentiation properties although they appear similar in the undifferentiated state

Molecular mechanisms of pluripotency and reprogramming

Pluripotent stem cells are able to form any terminally differentiated cell. They have opened new doors for experimental and therapeutic studies to understand early development and to cure degenerative diseases in a way not previously possible. Nevertheless, it remains important to resolve and define the mechanisms underlying pluripotent stem cells, as that understanding will impact strongly on future medical applications. The capture of pluripotent stem cells in a dish is bound to several landmark discoveries, from the initial culture and phenotyping of pluripotent embryonal carcinoma cells to the recent induction of pluripotency in somatic cells. On this developmental time line, key transcription factors, such as Oct4, Sox2 or Nanog, have been revealed not only to regulate but also to functionally induce pluripotency. These early master regulators of development control developmental signalling pathways that affect the cell cycle, regulate gene expression, modulate the epigenetic state and repair DNA damage. Besides transcription factors, microRNAs have recently been shown to play important roles in gene expression and are embedded into the regulatory network orchestrating cellular development. However, there are species-specific differences in pluripotent cells, such as surface marker expression and growth factor requirements. Such differences and their underlying developmental pathways require clear definition and have major impacts on the preclinical test bed of pluripotent cells

MKRN3 Interacts With Several Proteins Implicated in Puberty Timing but Does Not Influence GNRH1 Expression

Paternally-inherited loss-of-function mutations in makorin ring finger protein 3 gene (MKRN3) underlie central precocious puberty. To investigate the puberty-related mechanism(s) of MKRN3 in humans, we generated two distinct bi-allelic MKRN3 knock-out human pluripotent stem cell lines, Del 1 and Del 2, and differentiated them into GNRH1-expressing neurons. Both Del 1 and Del 2 clones could be differentiated into neuronal progenitors and GNRH1-expressing neurons, however, the relative expression of GNRH1 did not differ from wild type cells (P = NS). Subsequently, we investigated stable and dynamic protein-protein interaction (PPI) partners of MKRN3 by stably expressing it in HEK cells followed by mass spectrometry analyses. We found 81 high-confidence novel protein interaction partners, which are implicated in cellular processes such as insulin signaling, RNA metabolism and cell-cell adhesion. Of the identified interactors, 20 have been previously implicated in puberty timing. In conclusion, our stem cell model for generation of GNRH1 -expressing neurons did not offer mechanistic insight for the role of MKRN3 in puberty initiation. The PPI data, however, indicate that MKRN3 may regulate puberty by interacting with other puberty-related proteins. Further studies are required to elucidate the possible mechanisms and outcomes of these interactions.Peer reviewe

Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells

Gonadotropin-releasing hormone (GnRH) neurons provide a fundamental signal for the onset of puberty and subsequent reproductive functions by secretion of gonadotropin-releasing hormone. Their disrupted development or function leads to congenital hypogonadotropic hypogonadism (CHH). To model the development of human GnRH neurons, we generated a stable GNRH1-TdTomato reporter cell line in human pluripotent stem cells (hPSCs) using CRISPR-Cas9 genome editing. RNA-sequencing of the reporter clone, differentiated into GnRH neurons by dual SMAD inhibition and FGF8 treatment, revealed 6461 differentially expressed genes between progenitors and GnRH neurons. Expression of the transcription factor ISL1, one of the top 50 most upregulated genes in the TdTomato-expressing GnRH neurons, was confirmed in 10.5 gestational week-old human fetal GnRH neurons. Among the differentially expressed genes, we detected 15 genes that are implicated in CHH and several genes that are implicated in human puberty timing. Finally, FGF8 treatment in the neuronal progenitor pool led to upregulation of 37 genes expressed both in progenitors and in TdTomato-expressing GnRH neurons, which suggests upstream regulation of these genes by FGF8 signaling during GnRH neuron differentiation. These results illustrate how hPSC-derived human GnRH neuron transcriptomic analysis can be utilized to dissect signaling pathways and gene regulatory networks involved in human GnRH neuron development.This article has an associated First Person interview with the first author of the paper.Peer reviewe

A Novel Feeder-Free Culture System for Human Pluripotent Stem Cell Culture and Induced Pluripotent Stem Cell Derivation

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Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells

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Hyperglycosylated hCG activates LH/hCG-receptor with lower activity than hCG

While human chorionic gonadotropin (hCG) appears to have an essential role in early pregnancy, it is controversial whether the hyperglycosylated form of hCG (hCG-h), which is the major hCG isoform during the first 4-5 weeks of pregnancy, is able to activate LH/hCG receptor (LHCGR). To address this, we utilized different extensively characterized hCG and hCG beta reference reagents, cell culture- and urine-derived hCG-h preparations, and an in vitro reporter system for LHCGR activation. The WHO hCG reference reagent (99/688) was found to activate LHCGR with an EC50-value of 3.3 +/- 0.6 pmol/L (n = 9). All three studied hCG-h preparations were also able to activate LHCGR, but with a lower potency (EC50-values between 7.1 +/- 0.5 and 14 +/- 3 pmol/L, n = 5-11, for all P <0.05 as compared to the hCG reference). The activities of commercial urinary hCG (Pregnyl) and recombinant hCG (Ovitrelle) preparations were intermediate between those of the hCG reference and the hCG-h. These results strongly suggest that the hCG-h is functionally similar to hCG, although it has lower potency for LHCGR activation. Whether this explains the reduced proportion of hCG-h to hCG reported in patients developing early onset pre-eclampsia or those having early pregnancy loss remains to be determined.Peer reviewe