Lecture 11- haemopoetic dev Flashcards
what is haemotopoesis
the biol process which all blood cells are generated
what are the three mature blood cell types in verts
erythrocytes (rbc)
myeloids (innate immune syst)
lymphocytes (adaptive immune syst)
what is the function of erythrocytes and number produced daily
transport oxygen
2 million
system works non-stop to prouce cells (most common cell in body)
what is a subset of the myeloid
granulocytes
what are eg of myeloid
which one not granulocyte
neutrophil
eosinophil
basophil
macrophage (*)
what different about macrophages compared to rest of myeloid
life span days to years
in others only few days
what are some eg of lymphocytes
T cells (inc cytotoxi/helper/regulatory/memory) B cells (plasma/memory)
what the difference between b and t cells
b are less specific
what are megakaryocytes
another blood cell
fragments of which are platelets
each produces (2000-5000 platelets)
what is the stem cell all blood cell arise from
long term haemopoetic stem cell (LT HSC)
where ar LT hSC found
in bone marrow
the micro env conditions very complex and specific - not yet recreate in vivo
when are HSC created
in embryonic life
no de novo gen after birth
how does the emergence of the haemopoeitc system in the mouse embryo occur
in waves
where are the first blood cells in embryoinic life generated
yolk sac
when are the first blood cells generated in the embryo and what blood cells are they
9.5
b and t cell
what is the first wave of haemopoesis
at E7.25
primitive erythrocytes
macrophages
megakaryocytes
where in the yolk sac do first blood cells develop
blood island (formed from the migration of cells from primitive streak to yolk sac)
what are properties of primitive erythrocytes
gone at time of birth expr embryonic globins larger than definitive erythrocytes efficient distribution of oxygen at 8.5 in blood island only at 9.5 distributed everywhere
what is involved in the second wave of haemopoesis
in yolk sac at E8.25 () = generation of erythro-myeloid progenitors
in embryo at E9.5 = generation of t and b cell/lymphocytes progenitors
where are the erythro-myeloid progenitors generated and where do they migrate for maturation
yolk sac (E8.25) foetal liver (E11.5) give rise to definitive erythrocytes and all myeloid progenitors
what are tissue resident macrophages and where are they derived
highly specialised tissue specific macrophages
self renewing
generated during yolk sac haematopoiesis
then migrate to specific tissue and adopt specific fucntions
persist through adult life
maintained by self renewal
what is the third wave of haemopoiesis
at E10.5
HSC generated in embryo
what stages are HSC independent
up to E10.5
describe evidence that HSC not yolk sac derived
as visualised by staining at E8.25 thought were
but grafting experiment with chicks and quail (yolk sac and embryo) showed all cells derived from embryo
hsc only detected within the AGM region at E10.5 (inject from yolk sac - die/ inject from agm only survive)
where are hsc foudn in mie through utero
E10.5 - AGM
E 11 - foetal liver
E14 foetal spleen
E18 bone marrow
E11.25 yolk sac and placenta
what wave of haemopoeisis is called primitive haematopoeisis and what defintive
first wave - primitive
others - definitive
what is hemangioblast
a mesoderm precursor
gives ruse ti blood, endotheium and smooth muscle
how does hemangioblast generate blood cells
through a hemogenic endothelium intermiediate
what is ETV2 and where expr
a tf
expr in yolk sac mesoderm at the onset of gastrulation at E7.25
what is the role of ETV2 and how determined
master regulator of endothelial and blood prgrammes
mesoderm to hemangioblast trasnition
ko - no blood cells or vessels
what is SCL
a bHLH tf
phenotpye of SCL
identified at breakpoints in leukaemia
embryo deficiency - lethal
ko - no blood cells but have vessels
role of scl
required for generation of all blood cell types
hemangioblast to hemogenic endothelium
what us runx1
a core binding TF
phenotypes associated with RUNX1
most common gene translocated in leukaemia
deficient - lethal
deficient have primitive erythrocytes but no other cell types
have haemogenic endothelium but no blood cells
what is the role of RUNX1
endothelial to haematopoetic transition
