The Role of WNT-beta-Catenin Pathway in the Specification of Primitive and Definitive Hematopoiesis during Differentiation of Pluripotent Stem Cells

الموضوعات

طب

الملخص

The discovery of human pluripotent stem cells (hPSCs) has opened a new field calledregenerative medicine that offers new strategies for curing diseases and drug discovery.It also provides the means of regenerating disease-relevant cells in vitro for diseasemodeling, and the possibility of cell replacement therapy. Among the most promisingapplications of hPSCs technology is the generation of blood cells that can be used forengraftment or transfusion in the clinic. Generating engraftable hematopoietic stemcells from hPSCs in vitro can fulfill the promise of using hPSCs to cure human diseases.Making functional HSCs in vitro from hPSCs remains an elusive goal. There are keypathways that are misregulated during hPSCs differentiation, which could impair theengraftment potential of hPSCs. WNT signaling is needed in the early phase ofdifferentiation. However, evidence from mouse models and human development showthat WNT signaling is downregulated during the maturation of HSCs. Therefore, wehypothesize that mimicking the dynamics of WNT signaling temporally during thedifferentiation could improve the functional maturation of differentiated HPCs. To thisend, we have established an inducible gene activation system based on dCas9-VPR thatcan activate endogenous loci. We performed targeted activation of negative regulatorsof WNT. The system has shown promise in specific activation of WNT negativeregulators, AXIN2 and APC2, but it needs further optimization to be able to steer cellfate and obtain functional HSCs.

روابط وملفات

التعريف والنوع

رقم الوثيقة

0262abf6-16ea-47b3-bb34-6f6d5e0282a0

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf image

أسماء الملفات

0262abf6-16ea-47b3-bb34-6f6d5e0282a0_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":" Mo Li","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":" Samhan M. Alsolami","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

The Role of WNT-beta-Catenin Pathway in the Specification of Primitive and Definitive Hematopoiesis during Differentiation of Pluripotent Stem Cells

المحتوى والصفحات

عدد الصفحات

0

كلمات الباحثين

dCas9 Pluripotent Stem Cells

إشراف وإعداد

الإشراف

Mo Li

الإعداد

Samhan M. Alsolami

الاقتباسات الببليوغرافية