Geri Dön

Understanding the endothelial to hematopoietic transition in mouse development

Başlık çevirisi mevcut değil.

PDF İndir

  1. Tez No: 403056
  2. Yazar: ÖZGE VARGEL
  3. Danışmanlar: DR. CHRISTOPHE LANCRIN
  4. Tez Türü: Doktora
  5. Konular: Matematik, Mathematics
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2015
  8. Dil: İngilizce
  9. Üniversite: Ruprecht-Karls-Universität-Heidelberg
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 167

Özet

Özet yok.

Özet (Çeviri)

The endothelial to hematopoietic transition (EHT) is a key developmental event leading to the formation of blood stem and progenitor cells during embryogenesis. A small subset of cells called hemogenic endothelial cells (HE) undergoes the EHT by becoming pre-hematopoietic stem and progenitor cells (Pre-HSPC). Eventually after losing all their endothelial characteristics they become HSPC. Despite extensive studies on this process, there are several questions remaining: What are the differences between hemogenic and non hemogenic endothelial cells? How different is the EHT process in the aorta-gonad-mesonephros (AGM) generating mostly blood stem cells (self-renewing and generating all cell types] and the yolk sac (YS) producing mostly blood progenitors (non self-renewing and generating only a few cell types]? To address these questions, I used single cell transcriptomics because of the scarcity of the HE and the Pre-HSPC within the endothelial population in the AGM and YS. I examined the cells isolated at E9.0, E10.5 and E11.0 mouse embryos. I showed that the major endothelial population of AGM and YS is different from each other, which might be linked with their distinct hematopoietic program. I showed that the pre-HSPC in AGM and YS are transcriptionally alike suggesting that the different hematopoietic program between AGM and YS could be due to the microenvironment. Additionally, I identified a new population detected only in YS at E10.5 co-expressing endothelial and erythroid genes. The molecular mechanism of the EHT is still not understood. Since the TGFp signaling triggers a similar event during heart development called endothelial to mesenchymal transition (EndMT), we hypothesized that TGFp activity may play a similar role in EHT. When I activated the TGFp signaling by adding TGFp2 during in vitro EHT differentiation, I observed surprisingly a complete block of the hematopoiesis. When I inhibited it by adding the Tgfbrl inhibitor, it enhanced blood development. Additionally, the mRNA profile of the treated cells confirmed that inhibition of Alk5 is promoting the EHT, while the TGFp activation results in cells with a phenotype closer to cardiac and mesenchymal cells. Consequently, despite the fact that both EndMT and EHT lead to a loss of endothelial cell identity and the generation of mobile cells, our study suggests that the signaling events initiating both processes are different.

Benzer Tezler

  1. Tez No

    880257

    Aterosklerotik damar hastalığında endotel hücrelerindeki somatik gen mutasyonlarının rolü

    The role of somatic gene mutations on endothelial cells in atherosclerotic vascular disorder

    REYHAN KÜÇÜKKAYA

    Doktora

    Türkçe

    Türkçe

    2024

    Hematolojiİstanbul Üniversitesi

    Moleküler Biyoloji ve Genetik Ana Bilim Dalı

    PROF. DR. TUBA GÜNEL

  2. Tez No

    882920

    Detection of the red blood cell adhesion to the vascular endothelium using microfluidic chip in beta thalassemia patients

    Beta talasemi hastalarında mikroakışkan çip kullanılarak kırmızı kan hücrelerinin vasküler endotele yapışmasının tespiti

    NESLİHAN ÇİLEK

    Doktora

    İngilizce

    İngilizce

    2024

    Moleküler TıpKoç Üniversitesi

    Hücresel ve Moleküler Tıp Ana Bilim Dalı

    PROF. ÖZLEM YALÇIN SEYHAN

  3. Tez No

    170844

    A biochemical model for the interactions between tumor cell mass and vascular endothelial cells leading to angiogenesis

    Tümör hücre kütlesi ile vasküler endotel hücresi arası ilişkilerin doğurduğu anjiyogenezin biyokimyasal modellemesi

    MERYEM AYŞE YÜCEL

    Yüksek Lisans

    İngilizce

    İngilizce

    2005

    BiyokimyaBoğaziçi Üniversitesi

    Y.DOÇ.DR. ATA AKIN

    Y.DOÇ.DR. IŞIL AKSAN KURNAZ

  4. Tez No

    539985

    Investigation on the effects of mechanical forces on endothelial and monocytic cell behaviour by using microfluidic systems

    Mikroakışkan sistemler kullanılarak mekanik kuvvetlerin endotel ve monosit hücre davranışı üzerine etkilerinin incelenmesi

    SEMRA ZUHAL BİROL

    Doktora

    İngilizce

    İngilizce

    2018

    Bilim ve Teknolojiİstanbul Teknik Üniversitesi

    Nanobilim ve Nanomühendislik Ana Bilim Dalı

    PROF. DR. LEVENT TRABZON

  5. Tez No

    158035

    Serebral kavernoz malformasyonlarla (Cerebral cavernous malformation, CCM) mutasyona uğrayan KRIT1'in anjiogenik sinyal yolunun moleküler mekanizması

    The moleculer mechanism of angiogenic signaling pathway of KRIT1 mutated in cerebral cavernousmalformation

    ÖZLEM GÜZELOĞLU KAYIŞLI

    Doktora

    Türkçe

    Türkçe

    2004

    Tıbbi BiyolojiAkdeniz Üniversitesi

    Tıbbi Biyoloji ve Genetik Ana Bilim Dalı

    PROF.DR. GÜVEN LÜLECİ

Geri Dön