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Hematopoiesis in the allantois and chorion.

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Call No.	QP92 .Z45 2007
Author	Zeigler, Brandon.
Title	Hematopoiesis in the allantois and chorion.
Date	2007
Abstract	The placenta is the extra-embryonic tissue that mediates the exchange of oxygen and nutrients between the fetus and mother. It was shown that the placenta is a source of hematopoietic stem cells (HSCs). However, it is not known whether the placenta is a cell niche, where stem cells reside, expand, and are maintained; or whether HSCS arise de-novo from the placenta. I present work showing that two components of the placenta, the allantois and the chorion, have hematopoietic potential, suggesting that the placenta is a source of HSCs. We determined that Runx1, a transcription factor required for definitive hematopoiesis, was expressed in the allantois and the chorion before and after the onset of their fusion to form the placenta. We next utilized novel dissection techniques to isolate the chorion and allantois cleanly from the conceptus and cultured them directly onto feeder layers to generate hematopoietic cells. We also show that allantois explants lose hematopoietic potential when Runx1 is knocked out in vascular endothelium cadherin positive endothelial cells. These results indicate that allantoic cells must proceed thru an endothelial intermediate before they are committed to their hematopoietic fate. Finally, we present preliminary findings suggesting that the Hedgehog signal transduction pathway, which is required for Runx1 expression and hematopoiesis in zebrafish, does not regulate Runx1 expression in the allantois. Patched homolog 1 (Ptch1), a membrane protein receptor for hedgehog, is expressed at the allantoic base but the majority of allantoic cells do not express Ptch1. We also show that allantoic explants cultured in the presence of a Hedgehog signaling blocker, cyclopamine, maintained Runx1 expression, suggesting a different molecular pathway induces the hematopoietic program in the allantois.
Description	x, 133 leaves : col. ill. 28 cm.
Format	application/pdf
Advisor	Nancy A. Speck
Subject	Hematopoietic stem cells. ; Transcription factors. Placenta -- Cytology. Chorion -- Cytology. ; Cellular signal transduction.
College	Dartmouth Medical School -- Department of Biochemistry.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1695

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Hematopoiesis in the allantois and chorion.

Hematopoiesis in the allantois and chorion.