Alexander Medvinsky
Professor in Haematopoietic Stem Cell Biology
- Centre for Regenerative Medicine
- Institute of Regeneration and Repair
Contact details
- Tel: 0131 651 9556
- Email: a.medvinsky@ed.ac.uk
Address
- Street
-
Centre for Regenerative Medicine,
Institute for Regeneration and Repair,
The University of Edinburgh,
Edinburgh BioQuarter,
5 Little France Drive, - City
- Edinburgh
- Post code
- EH16 4UU
Current PhD students supervised
Nneka Concilia Nnadi
Adelle Greene
Research summary
Ontogeny of haematopoietic stem cells
Haematopoietic stem cells (HSCs) developing in the embryo ultimately give rise to the adult haematopoietic system. The main direction of our research is to investigate cellular and molecular mechanisms involved in the generation and expansion of primitive HSCs in the mammalian embryo.
Aims and areas of interest
Our specific aims are to
- Phenotypically characterize and visualize primary definitive HSCs in the early embryo
- Identify embryonic ancestor cells which develop into HSCs
- Identify routes and mechanisms of hematopoietic stem cell migration
- Identify and characterize transcription and growth factors as well as extracellular signaling and matrix molecules responsible for the process of initiation, expansion and migration of HSCs.
- Based on the knowledge of mechanisms underlying development of HSCs in vivo, develop new protocols for generation of definitive long-term repopulating HSCs from ES cells (so far attempts to achieve this by different laboratories without employing genetic intervention have been unsuccessful).
Background
Haematopoietic stem cells (HSCs) developing in the embryo ultimately give rise to the adult haematopoietic system. The main direction of our research is to investigate cellular and molecular mechanisms involved in the generation and expansion of primitive hematopoietic stem cells (HSC) in the mammalian embryo.
Approach and progress
We broadly use methods to perform embryo manipulations and experimental haematology techniques such as advanced cell culture and flow cytometry for the analysis of the early biology of HSCs, including investigating the lineage relationship between endothelial and HSC cells. We have recently identified a specific niche for HSC development in the AGM region. We have developed new culture methods which allow us to dramatically expand HSCs in vitro and analyse intercellular interactions involved in HSC development. Several transgenic/ knockout/reporter mice have been generated in this laboratory, which we use for genetic analysis of HSC development (e.g. Runx1, Flk1, HoxB4 etc.). Microarray analysis is used for gene expression profiling in sites of embryonic development of HSCs. We are applying our functional analysis of HSC development in the embryo to develop new protocols enabling the in vitro generation of HSCs from ES cells.
Affiliated research centres
-
Vast self-renewal potential of human AGM region HSCs dramatically declines in the umbilical cord blood
In:
Stem Cell Reports
Research output: Contribution to Journal › Article (Accepted/In press) -
Multi-layered spatial transcriptomics identify secretory factors promoting hematopoietic stem cell emergence in human development
In:
Cell Stem Cell
Research output: Contribution to Journal › Article (Accepted/In press) -
Single cell analyses and machine learning define hematopoietic progenitor and HSC-like cells derived from human PSCs.
In:
Blood
Research output: Contribution to Journal › Article (Published) -
Analysis of the spatiotemporal development of hematopoietic stem and progenitor cells in the early human embryo
(13 pages)
In:
Stem Cell Reports, vol. 12, pp. 1056-1068
DOI: https://doi.org/10.1016/j.stemcr.2019.03.003
Research output: Contribution to Journal › Article (Published) -
Analysis of Runx1 Using Induced Gene Ablation Reveals Its Essential Role in Pre-liver HSC Development and Limitations of an In Vivo Approach
(11 pages)
In:
Stem Cell Reports, vol. 11, pp. 784-794
DOI: https://doi.org/10.1016/j.stemcr.2018.08.004
Research output: Contribution to Journal › Article (Published) -
Cellular Origin and Functional Relevance of Collagen I Production in the Kidney
(15 pages)
In:
Journal of the American Society of Nephrology, vol. 29, pp. 1859-1873
DOI: https://doi.org/10.1681/ASN.2018020138
Research output: Contribution to Journal › Article (Published) -
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation
(21 pages)
In:
Journal of Experimental Medicine
DOI: https://doi.org/10.1084/jem.20162012
Research output: Contribution to Journal › Article (Published) -
Human haematopoietic stem cell development: From the embryo to the dish: From the embryo to the dish
(15 pages)
In:
Development, vol. 144, pp. 2323-2337
DOI: https://doi.org/10.1242/dev.134866
Research output: Contribution to Journal › Review article (Published) -
Cardiosphere Derived Cells Require Endoglin For Paracrine-Mediated Angiogenesis
(12 pages)
In:
Stem Cell Reports, vol. 8, pp. 1287-1298
DOI: https://doi.org/10.1016/j.stemcr.2017.04.015
Research output: Contribution to Journal › Article (Published) -
Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture
In:
Stem Cell Reports
DOI: https://doi.org/10.1016/j.stemcr.2017.04.003
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Blood flow controls bone vascular function and osteogenesis
In:
Nature Communications, vol. 7, pp. 13601
DOI: https://doi.org/10.1038/ncomms13601
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Developing HSCs become Notch independent by the end of maturation in the AGM region
(11 pages)
In:
Blood, vol. 128, pp. 1567-157
DOI: https://doi.org/10.1182/blood-2016-03-708164
Research output: Contribution to Journal › Article (Published) -
Ontogeny of the Haematopoietic System
(14 pages)
DOI: https://doi.org/10.1016/B978-0-12-374279-7.01002-X
Research output: › Entry for encyclopedia/dictionary (E-pub ahead of print) -
Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver
In:
Development, pp. 1284-1289
DOI: https://doi.org/10.1242/dev.131193
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Deletion of Pten of CD45-expressing cells leads to development of T-cell lymphoblastic lymphoma but not myeloid malignancies
In:
Blood, vol. 127, pp. 1907-1911
DOI: https://doi.org/10.1182/blood-2015-09-669036
Research output: Contribution to Journal › Article (Published) -
Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells
(13 pages)
In:
Nature Communications, vol. 7
DOI: https://doi.org/10.1038/ncomms10784
Research output: Contribution to Journal › Article (Published) -
The European Hematology Association Roadmap for European Hematology Research. A Consensus Document
In:
Haematologica
DOI: https://doi.org/10.3324/haematol.2015.136739
Research output: Contribution to Journal › Article (Published) -
Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation
In:
BMC Developmental Biology, vol. 15
DOI: https://doi.org/10.1186/s12861-015-0084-7
Research output: Contribution to Journal › Article (Published) -
In search of human hematopoietic stem cell identity
(2 pages)
In:
Cell Stem Cell, vol. 16, pp. 5-6
DOI: https://doi.org/10.1016/j.stem.2014.12.010
Research output: Contribution to Journal › Editorial (Published) -
Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary
(16 pages)
In:
Experimental Cell Research, vol. 332, pp. 163-178
DOI: https://doi.org/10.1016/j.yexcr.2015.01.010
Research output: Contribution to Journal › Article (Published)