Hematopoietic Stem Cell Arrival Triggers Dynamic Remodeling of the Perivascular Niche

نویسندگان

  • Owen J. Tamplin
  • Ellen M. Durand
  • Logan A. Carr
  • Sarah J. Childs
  • Elliott J. Hagedorn
  • Pulin Li
  • Amanda D. Yzaguirre
  • Nancy A. Speck
  • Leonard I. Zon
چکیده

Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish. This allowed us to perform high-resolution live imaging on endogenous HSPCs not currently possible in mammalian bone marrow. Using this system, we have uncovered distinct interactions between single HSPCs and their niche. When an HSPC arrives in the perivascular niche, a group of endothelial cells remodel to form a surrounding pocket. This structure appears conserved in mouse fetal liver. Correlative light and electron microscopy revealed that endothelial cells surround a single HSPC attached to a single mesenchymal stromal cell. Live imaging showed that mesenchymal stromal cells anchor HSPCs and orient their divisions. A chemical genetic screen found that the compound lycorine promotes HSPC-niche interactions during development and ultimately expands the stem cell pool into adulthood. Our studies provide evidence for dynamic niche interactions upon stem cell colonization. PAPERFLICK:

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Targeting of c-kit+ hematopoietic progenitor cells prevents hypoxic pulmonary hypertension

Hematopoietic c-kit+ progenitor cells may contribute to pulmonary vascular remodeling and pulmonary hypertension. Stromal derived factor-1 (SDF-1/CXCL12) and its receptors CXCR4 and CXCR7 have been shown to be critical for homing and mobilization of hematopoietic c-kit+ progenitor cells in the perivascular niche. We administered AMD3100, a CXCR4 antagonist, and CCX771, a CXCR7 antagonist, to ch...

متن کامل

تاثیر آشیانه‌های جفتی شبیه‌سازی شده با داربست پلی لاکتیک اسید در تکثیر سلول‌های بنیادی خونساز مشتق از بافت جفت انسانی

Background and Objective: Nowadays, although umbilical cord blood is a commonly used source of hematopoietic stem cell, its low frequency of these cells is the main factor limiting its clinical application. The transplantation of hematopoietic stem cells derived from placenta tissue along with umbilical cord blood cells of the same sample may be an appropriate approach to solve this problem. In...

متن کامل

The Perivascular Niche and Self-Renewal of Stem Cells

Postnatal stem cells are typically found in niches that provide signaling cues to maintain their self-renewal and multipotency. While stem cell populations may serve distinct purposes within their tissue of origin, understanding the conserved biology of stem cells and their respective niches provides insights to the behavior of these cells during homeostasis and tissue repair. Here, we discuss ...

متن کامل

Making sense of hematopoietic stem cell niches.

The hematopoietic stem cell (HSC) niche commonly refers to the pairing of hematopoietic and mesenchymal cell populations that regulate HSC self-renewal, differentiation, and proliferation. Anatomic localization of the niche is a dynamic unit from the developmental stage that allows proliferating HSCs to expand before they reach the bone marrow where they adopt a quiescent phenotype that protect...

متن کامل

Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche.

Perivascular mesenchymal stem and progenitor cells (MSPCs) are critical for forming a healthy hematopoietic stem cell (HSC) niche. However, the interactions and influence of acute myelogenous leukemia (AML) stem cells with the microenvironment remain largely unexplored. We have unexpectedly found that neuropathy of the sympathetic nervous system (SNS) promotes leukemic bone marrow infiltration ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cell

دوره 160  شماره 

صفحات  -

تاریخ انتشار 2015